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  • (2S,4S,5S,7S)-7-(3-(3-Methoxypropoxy)-4-methoxybenzyl)-5-amino-N-(2-carbamoyl-2-methylpropyl)-4-hydroxy-2-isopropyl-8-methylnonanamide hydrochloride

    Cas No: 173334-57-1

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  • Henan Allgreen Chemical Co.,Ltd
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  • 173334-57-1 Structure
  • Basic information

    1. Product Name: Aliskiren
    2. Synonyms: (2S,4S,5S,7S)-5-Amino-N-(2-carbamoyl-2-methylpropyl)-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide;(aS,S,dS,zS)-d-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)--hydroxy-4-methoxy-3-(3-methoxypropoxy)-α,z-bis(1-methylethyl)benzeneoctanamide;CGP 60536;CGP60536B;Rasilez;SPP 100;Tekturna;(aS,S,dS,zS)-d-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)--hydroxy-4-methoxy-3-(3-methoxypropoxy)-a,z-bis(1-methylethyl)benzeneoctanamide
    3. CAS NO:173334-57-1
    4. Molecular Formula: C30H53N3O6
    5. Molecular Weight: 551.76
    6. EINECS: 1308068-626-2
    7. Product Categories: Chemical Amines;Amines;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Aliskiren intermediates;API
    8. Mol File: 173334-57-1.mol
    9. Article Data: 32
  • Chemical Properties

    1. Melting Point: 98-99 °C
    2. Boiling Point: 748.4 °C at 760 mmHg
    3. Flash Point: 406.4 °C
    4. Appearance: /
    5. Density: 1.067 g/cm3
    6. Vapor Pressure: 1.12E-24mmHg at 25°C
    7. Refractive Index: N/A
    8. Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
    9. Solubility: N/A
    10. PKA: 9.49(at 25℃)
    11. CAS DataBase Reference: Aliskiren(CAS DataBase Reference)
    12. NIST Chemistry Reference: Aliskiren(173334-57-1)
    13. EPA Substance Registry System: Aliskiren(173334-57-1)
  • Safety Data

    1. Hazard Codes: N/A
    2. Statements: N/A
    3. Safety Statements: N/A
    4. WGK Germany:
    5. RTECS:
    6. HazardClass: N/A
    7. PackingGroup: N/A
    8. Hazardous Substances Data: 173334-57-1(Hazardous Substances Data)

173334-57-1 Usage

Description

Aliskiren, also known as Tekturna or Rasilez, is a first-in-class antihypertensive drug that acts by directly inhibiting the enzyme renin. It was the first renin inhibitor introduced into the U.S. market and was approved by the FDA in 2007 for the management of hypertension. Aliskiren is a monomethoxybenzene compound with a 3-methoxypropoxy group at the 2-position and a multi-substituted branched alkyl substituent at the 4-position.

Uses

Used in Pharmaceutical Industry:
Aliskiren is used as an antihypertensive agent for the management of hypertension. It works by inhibiting the enzyme renin, which is the rate-limiting step in the renin-angiotensin-aldosterone system (RAAS). This inhibition results in reduced levels of angiotensin I, angiotensin II, and aldosterone, all of which contribute to the antihypertensive effect. Aliskiren is indicated for oral administration either as monotherapy or in combination with other antihypertensive agents.
The most common side effect of aliskiren is diarrhea, particularly with doses higher than 300mg daily. Unlike ACE inhibition, direct inhibition of renin does not increase bradykinin levels, which are thought to be responsible for the angioderma and cough that occur commonly during treatment with ACE inhibitors.

Originator

Novartis (Switzerland)

Check Digit Verification of cas no

The CAS Registry Mumber 173334-57-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,7,3,3,3 and 4 respectively; the second part has 2 digits, 5 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 173334-57:
(8*1)+(7*7)+(6*3)+(5*3)+(4*3)+(3*4)+(2*5)+(1*7)=131
131 % 10 = 1
So 173334-57-1 is a valid CAS Registry Number.
InChI:InChI=1/C30H53N3O6.ClH/c1-19(2)22(14-21-10-11-26(38-8)27(15-21)39-13-9-12-37-7)16-24(31)25(34)17-23(20(3)4)28(35)33-18-30(5,6)29(32)36;/h10-11,15,19-20,22-25,34H,9,12-14,16-18,31H2,1-8H3,(H2,32,36)(H,33,35);1H/t22-,23-,24-,25-;/m0./s1

173334-57-1SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 18, 2017

Revision Date: Aug 18, 2017

1.Identification

1.1 GHS Product identifier

Product name Aliskiren

1.2 Other means of identification

Product number -
Other names SPP 100

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:173334-57-1 SDS

173334-57-1Synthetic route

tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate
173338-07-3

tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Stage #1: tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate With hydrogenchloride In dichloromethane at 0 - 5℃;
Stage #2: With sodium hydroxide In dichloromethane pH=9;
100%
With hydrogenchloride In 1,4-dioxane at 0℃; Inert atmosphere;99%
With hydrogenchloride; water In ethyl acetate at 20℃; for 0.0833333h; Flow reactor;96%
(1S,2S,4S)-4-(2-carbamoyl-2-methylpropyl-carbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl-carbamic acid benzyl ester
1236549-06-6

(1S,2S,4S)-4-(2-carbamoyl-2-methylpropyl-carbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl-carbamic acid benzyl ester

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
With 10% palladium on activated charcoal; hydrogen97%
With 5%-palladium/activated carbon; hydrogen In tert-butyl methyl ether at 25℃; under 2280.15 Torr; for 16h;86%
With 5%-palladium/activated carbon; hydrogen In tert-butyl methyl ether at 25℃; under 2280.15 Torr; for 16h;86%
Stage #1: (1S,2S,4S)-4-(2-carbamoyl-2-methylpropyl-carbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl-carbamic acid benzyl ester With hydrogen; acetic acid; palladium 10% on activated carbon In ethanol at 20℃; under 760.051 Torr;
Stage #2: With sodium hydroxide In ethanol pH=10;
Stage #1: (1S,2S,4S)-4-(2-carbamoyl-2-methylpropyl-carbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl-carbamic acid benzyl ester With hydrogen; acetic acid; palladium 10% on activated carbon In ethanol at 20℃; under 760.051 Torr;
Stage #2: With sodium hydroxide In ethanol; water pH=10;
C37H59N3O6

C37H59N3O6

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
With hydrogen; ethanolamine; 10% palladium on activated carbon In methanol at 20℃; under 760.051 Torr; for 3h;87%
aminopivalinamide
324763-51-1

aminopivalinamide

C29H49NO6S

C29H49NO6S

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
With 2-hydroxypyridin; hydrogenchloride; triethylamine In methanol at 80℃;68%
3-amino-2,2-dimethylpropionamide ammonium chloride

3-amino-2,2-dimethylpropionamide ammonium chloride

1,1-dimethylethyl[(1S,3S)-3-[{4-methoxy-3-(3-methoxypropoxy)phenyl}methyl]-4-methyl-1-[tetrahydro-4-(1-methylethyl)-5-oxo-2-furanyl]pentyl]carbamate

1,1-dimethylethyl[(1S,3S)-3-[{4-methoxy-3-(3-methoxypropoxy)phenyl}methyl]-4-methyl-1-[tetrahydro-4-(1-methylethyl)-5-oxo-2-furanyl]pentyl]carbamate

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Stage #1: 3-amino-2,2-dimethylpropionamide ammonium chloride; 1,1-dimethylethyl[(1S,3S)-3-[{4-methoxy-3-(3-methoxypropoxy)phenyl}methyl]-4-methyl-1-[tetrahydro-4-(1-methylethyl)-5-oxo-2-furanyl]pentyl]carbamate; sodium 2-ethylhexanoic acid at 120℃; for 1h;
Stage #2: With amine HCl
Stage #3: With NaA Product distribution / selectivity;
40%
(2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide

(2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
With palladium on activated charcoal; hydrogen In methanol at 20℃; for 3h;38%
(2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide
324763-47-5

(2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
With hydrogenchloride; hydrogen; palladium on activated charcoal In methanol
With 1% Pd/C; hydrogen In ethanol
In methanol
With hydrogen; ethanolamine; palladium 10% on activated carbon In isopropyl alcohol for 3h; Product distribution / selectivity;
With palladium 10% on activated carbon; ammonia; hydrogen In ethanol at 20℃; under 5250.53 Torr;
(2-carbamoyl-2-methylpropyl)carbamic acid benzyl ester
666844-61-7

(2-carbamoyl-2-methylpropyl)carbamic acid benzyl ester

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: H2 / Pd()OH)2/C
2: 65 percent / 2-hydroxypyridine; Et3N
3: TMSCl; phenol / CH2Cl2
View Scheme
(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester
172900-83-3

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: Mg
2: 23 percent / H2 / Pd(OH)2/C
3: 38 percent / TPAP; NMMO
4: 65 percent / 2-hydroxypyridine; Et3N
5: TMSCl; phenol / CH2Cl2
View Scheme
(2R,5S)-3,6-diethoxy-2-isopropyl-5-((S)-2-(4-methoxy-3-(3-methoxypropoxy)benzyl)-3-methylbutyl)-2,5-dihydropyrazine
866030-33-3

(2R,5S)-3,6-diethoxy-2-isopropyl-5-((S)-2-(4-methoxy-3-(3-methoxypropoxy)benzyl)-3-methylbutyl)-2,5-dihydropyrazine

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 9 steps
1: HCl / acetonitrile
2: Et3N
3: NaBH4 / ethanol
4: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
5: Mg
6: 23 percent / H2 / Pd(OH)2/C
7: 38 percent / TPAP; NMMO
8: 65 percent / 2-hydroxypyridine; Et3N
9: TMSCl; phenol / CH2Cl2
View Scheme
tert-butyl {(1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl}carbamate
866030-35-5

tert-butyl {(1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl}carbamate

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 65 percent / 2-hydroxypyridine; Et3N
2: TMSCl; phenol / CH2Cl2
View Scheme
Multi-step reaction with 2 steps
1.1: triethylamine; 2-hydroxypyridin / tert-butyl methyl ether / 18 h / 80 °C
2.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C
2.2: pH 10
View Scheme
Multi-step reaction with 2 steps
1.1: triethylamine; 2-hydroxypyridin / 36 h / 60 - 65 °C
2.1: hydrogenchloride / dichloromethane; water / 3 h / 0 - 5 °C
2.2: 0 - 5 °C
View Scheme
((1S,2S,4S)-2-hydroxy-4-hydroxymethyl-1-((S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl)-5-methyl-hexyl)-carbamic acid tert-butyl ester
866030-34-4

((1S,2S,4S)-2-hydroxy-4-hydroxymethyl-1-((S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl)-5-methyl-hexyl)-carbamic acid tert-butyl ester

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 38 percent / TPAP; NMMO
2: 65 percent / 2-hydroxypyridine; Et3N
3: TMSCl; phenol / CH2Cl2
View Scheme
(1S,4S,2'S)-(4-benzyloxymethyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-5-methylhexyl)carbamic acid tert-butyl ester

(1S,4S,2'S)-(4-benzyloxymethyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-5-methylhexyl)carbamic acid tert-butyl ester

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: 23 percent / H2 / Pd(OH)2/C
2: 38 percent / TPAP; NMMO
3: 65 percent / 2-hydroxypyridine; Et3N
4: TMSCl; phenol / CH2Cl2
View Scheme
isovanillin
621-59-0

isovanillin

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 17 steps
1: 98 percent / K2CO3 / acetonitrile
2: NaBH4 / ethanol
3: PBr3 / CH2Cl2
4: 76 percent / LiHMDS / tetrahydrofuran
5: 81 percent / LiOH; H2O2
6: 95 percent / LAH / tetrahydrofuran
7: 97 percent / PPh3; NBS / CH2Cl2
8: 68 percent / n-BuLi
9: HCl / acetonitrile
10: Et3N
11: NaBH4 / ethanol
12: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
13: Mg
14: 23 percent / H2 / Pd(OH)2/C
15: 38 percent / TPAP; NMMO
16: 65 percent / 2-hydroxypyridine; Et3N
17: TMSCl; phenol / CH2Cl2
View Scheme
aminopivalinamide
324763-51-1

aminopivalinamide

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 65 percent / 2-hydroxypyridine; Et3N
2: TMSCl; phenol / CH2Cl2
View Scheme
2-cyano-2-methylpropanamide
7505-93-3

2-cyano-2-methylpropanamide

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1.1: LAH / tetrahydrofuran
1.2: Et3N
2.1: H2 / Pd()OH)2/C
3.1: 65 percent / 2-hydroxypyridine; Et3N
4.1: TMSCl; phenol / CH2Cl2
View Scheme
Multi-step reaction with 3 steps
1: hydrogen; ammonia / raney nickel / methanol / 14 h / 40 - 45 °C / 2942.29 Torr
2: triethylamine; 2-hydroxypyridin / 16 h / 85 - 90 °C
3: hydrogen; ethanolamine / palladium 10% on activated carbon / isopropyl alcohol / 3 h
View Scheme
Multi-step reaction with 2 steps
1.1: hydrogen; ammonia / raney nickel / methanol / 14 h / 40 - 45 °C / 2942.29 Torr
2.1: 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone / 4 h / 75 - 80 °C
2.2: 15 h / 85 - 90 °C
2.3: 3 h
View Scheme
Multi-step reaction with 3 steps
1.1: ammonia / Raney nickel / methanol / 25 - 35 °C / Autoclave
1.2: 10 h / 60 - 65 °C / 5149.01 - 5884.58 Torr
2.1: triethylamine; 2-hydroxypyridin
3.1: hydrogenchloride / water; acetone / 20 °C
3.2: pH 8 - 9
View Scheme
(R)-4-benzyl-3-(3-methylbutyryl)oxazolidin-2-one
145589-03-3

(R)-4-benzyl-3-(3-methylbutyryl)oxazolidin-2-one

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 14 steps
1: 76 percent / LiHMDS / tetrahydrofuran
2: 81 percent / LiOH; H2O2
3: 95 percent / LAH / tetrahydrofuran
4: 97 percent / PPh3; NBS / CH2Cl2
5: 68 percent / n-BuLi
6: HCl / acetonitrile
7: Et3N
8: NaBH4 / ethanol
9: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
10: Mg
11: 23 percent / H2 / Pd(OH)2/C
12: 38 percent / TPAP; NMMO
13: 65 percent / 2-hydroxypyridine; Et3N
14: TMSCl; phenol / CH2Cl2
View Scheme
Multi-step reaction with 9 steps
1: 50 percent / TiCl4 / CH2Cl2
2: 82 percent / LiOH; H2O2
3: 86 percent / LAH / tetrahydrofuran
4: 61 percent / PPh3; NBS / CH2Cl2
5: Mg
6: 23 percent / H2 / Pd(OH)2/C
7: 38 percent / TPAP; NMMO
8: 65 percent / 2-hydroxypyridine; Et3N
9: TMSCl; phenol / CH2Cl2
View Scheme
Multi-step reaction with 13 steps
1.1: lithium hexamethyldisilazane / -78 °C / Inert atmosphere; Large scale
1.2: -78 °C / Inert atmosphere; Large scale
1.3: Inert atmosphere; Large scale
2.1: lithium aluminium tetrahydride / tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere
3.1: triethylamine / toluene / 1.5 h / 0 - 20 °C / Inert atmosphere
4.1: sodium iodide / acetonitrile / 12 h / Inert atmosphere; Reflux
5.1: lithium hydride / N,N-dimethyl acetamide / 1 h / 60 °C / Inert atmosphere
5.2: 48 h / 60 °C / Inert atmosphere
6.1: dmap; triethylamine / 3 h / 20 °C / Inert atmosphere
7.1: trifluoroacetic acid / 1 h / 20 °C / Inert atmosphere
8.1: (R)-(-)-4,12-bis(diphenylphosphino)[2.2]paracyclophane(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; hydrogen; triethylamine / methanol / 24 h / 60 °C / 22502.3 Torr / Inert atmosphere; Large scale
9.1: diphenyl phosphoryl azide; triethylamine / toluene / 1 h / 80 °C / Inert atmosphere
9.2: 8 h / Inert atmosphere; Reflux
10.1: hydrogenchloride; water / ethanol / 48 h / 70 °C / Inert atmosphere
11.1: hydrogen; palladium 10% on activated carbon / methanol / 12 h / 20 °C / Inert atmosphere
11.2: 2 h / 20 °C / Inert atmosphere
12.1: 2-Ethylhexanoic acid / n-heptane / 8 h / 70 °C / Inert atmosphere
13.1: hydrogenchloride / dichloromethane / 3 h / -10 - 0 °C / Inert atmosphere
View Scheme
Multi-step reaction with 14 steps
1.1: diisopropylamine; n-butyllithium / tetrahydrofuran; hexane / 2 h / -78 °C / Inert atmosphere
1.2: 20 h / -78 - 20 °C
2.1: water; dihydrogen peroxide; lithium hydroxide / tetrahydrofuran / 3 h / 0 - 20 °C
3.1: lithium aluminium tetrahydride / tetrahydrofuran / 6.5 h / 0 °C / Inert atmosphere; Reflux
4.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1.5 h / 50 - 60 °C / Inert atmosphere
4.2: 20 °C
5.1: magnesium / tetrahydrofuran / 0.5 h / Inert atmosphere
5.2: -78 - 20 °C / Inert atmosphere
6.1: triethylamine; chlorotriethylstannane / 1,4-dioxane / 2 h / 0 °C
6.2: 20 °C
7.1: sodium periodate; ruthenium trichloride / acetonitrile / 0 - 20 °C
8.1: copper(II) sulfate / dichloromethane / 5 h / Reflux
9.1: boron trifluoride diethyl etherate / dichloromethane / 0.33 h / -78 - 20 °C
9.2: 5 h / 20 °C
10.1: diisobutylaluminium hydride / toluene / 2.5 h / -20 °C
11.1: magnesium / 0.5 h / Inert atmosphere
11.2: 3 h / -78 - 20 °C / Inert atmosphere
12.1: 10 wt% Pd(OH)2 on carbon; hydrogen / ethanol
13.1: 4-methylmorpholine N-oxide; tetrapropylammonium perruthennate / dichloromethane / 2 h / 20 °C / Inert atmosphere; Molecular sieve
14.1: triethylamine; 2-hydroxypyridin; hydrogenchloride / methanol / 80 °C
View Scheme
4-methoxy-3-(3-methoxypropoxy)benzaldehyde
172900-75-3

4-methoxy-3-(3-methoxypropoxy)benzaldehyde

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 16 steps
1: NaBH4 / ethanol
2: PBr3 / CH2Cl2
3: 76 percent / LiHMDS / tetrahydrofuran
4: 81 percent / LiOH; H2O2
5: 95 percent / LAH / tetrahydrofuran
6: 97 percent / PPh3; NBS / CH2Cl2
7: 68 percent / n-BuLi
8: HCl / acetonitrile
9: Et3N
10: NaBH4 / ethanol
11: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
12: Mg
13: 23 percent / H2 / Pd(OH)2/C
14: 38 percent / TPAP; NMMO
15: 65 percent / 2-hydroxypyridine; Et3N
16: TMSCl; phenol / CH2Cl2
View Scheme
Multi-step reaction with 13 steps
1.1: sodium tetrahydroborate / tetrahydrofuran / 0 - 30 °C
1.2: pH 2
2.1: phosphorus tribromide / dichloromethane / 2.17 h / 0 - 5 °C
3.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / -70 °C / Inert atmosphere
3.2: -70 - 5 °C
4.1: dihydrogen peroxide; lithium hydroxide monohydrate / water; tetrahydrofuran / 0 - 30 °C
5.1: sodium tetrahydroborate / tetrahydrofuran / 1 h / 0 - 5 °C / Inert atmosphere
5.2: 5.75 h / 0 - 30 °C
6.1: N-chloro-succinimide; triphenylphosphine / dichloromethane / 5.5 h / -40 - 30 °C
7.1: magnesium; ethylene dibromide / tetrahydrofuran / 4.17 h / 63 - 68 °C / Inert atmosphere
7.2: 12.5 h / 0 - 5 °C
8.1: water; lithium hydroxide / tetrahydrofuran; methanol / 26 h / 65 - 70 °C
8.2: 0.5 h / 0 - 5 °C
9.1: hydrogenchloride / 1,1-dichloroethane; water / 0 - 5 °C / pH 2.5
9.2: 14.25 h / 0 - 30 °C
10.1: N-Bromosuccinimide; phosphoric acid / water; tetrahydrofuran / 1.25 h / 0 - 5 °C
11.1: sodium azide / ethylene glycol / 20 h / 80 - 85 °C
12.1: triethylamine; 2-hydroxypyridin / 16 h / 85 - 90 °C
13.1: hydrogen; ethanolamine / palladium 10% on activated carbon / isopropyl alcohol / 3 h
View Scheme
Multi-step reaction with 10 steps
1.1: sodium tetrahydroborate / tetrahydrofuran / 0 - 30 °C
1.2: pH 2
2.1: phosphorus tribromide / dichloromethane / 2.17 h / 0 - 5 °C
3.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / -70 °C / Inert atmosphere
3.2: -70 - 5 °C
4.1: sodium tetrahydroborate / tetrahydrofuran / 0 - 15 °C
4.2: 11 h / 60 - 65 °C
5.1: N-chloro-succinimide; triphenylphosphine / dichloromethane / 5.5 h / -40 - 30 °C
6.1: magnesium; ethylene dibromide / tetrahydrofuran / 4.17 h / 63 - 68 °C / Inert atmosphere
6.2: 12.5 h / 0 - 5 °C
7.1: water; lithium hydroxide / tetrahydrofuran; methanol / 26 h / 65 - 70 °C
7.2: 0.5 h / 0 - 5 °C
8.1: hydrogenchloride / 1,1-dichloroethane; water / 0 - 5 °C / pH 2.5
8.2: 14.25 h / 0 - 30 °C
9.1: N-Bromosuccinimide; phosphoric acid / water; tetrahydrofuran / 1.25 h / 0 - 5 °C
10.1: 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone / 4 h / 75 - 80 °C
10.2: 15 h / 85 - 90 °C
10.3: 3 h
View Scheme
(R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutanol
172900-70-8

(R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutanol

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 11 steps
1: 97 percent / PPh3; NBS / CH2Cl2
2: 68 percent / n-BuLi
3: HCl / acetonitrile
4: Et3N
5: NaBH4 / ethanol
6: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
7: Mg
8: 23 percent / H2 / Pd(OH)2/C
9: 38 percent / TPAP; NMMO
10: 65 percent / 2-hydroxypyridine; Et3N
11: TMSCl; phenol / CH2Cl2
View Scheme
Multi-step reaction with 7 steps
1: 70 percent / SOCl2; pyridine
2: Mg; BrCH2CH2Br / tetrahydrofuran / 20 °C
3: H2 / [Ru2Cl4((S)-BINAP)]NEt3 / methanol / 40 h / 40 °C / 37503 Torr
4: NEt3 / CH2Cl2
5: 85 percent / NaN3; 15-crown-6; DMPU
6: 59 percent / 2-OH-pyridine; NEt3
7: H2; aq. HCl / Pd/C / methanol
View Scheme
Multi-step reaction with 8 steps
1.1: N-chloro-succinimide; triphenylphosphine / dichloromethane / 5.5 h / -40 - 30 °C
2.1: magnesium; ethylene dibromide / tetrahydrofuran / 4.17 h / 63 - 68 °C / Inert atmosphere
2.2: 12.5 h / 0 - 5 °C
3.1: water; lithium hydroxide / tetrahydrofuran; methanol / 26 h / 65 - 70 °C
3.2: 0.5 h / 0 - 5 °C
4.1: hydrogenchloride / 1,1-dichloroethane; water / 0 - 5 °C / pH 2.5
4.2: 14.25 h / 0 - 30 °C
5.1: N-Bromosuccinimide; phosphoric acid / water; tetrahydrofuran / 1.25 h / 0 - 5 °C
6.1: sodium azide / ethylene glycol / 20 h / 80 - 85 °C
7.1: triethylamine; 2-hydroxypyridin / 16 h / 85 - 90 °C
8.1: hydrogen; ethanolamine / palladium 10% on activated carbon / isopropyl alcohol / 3 h
View Scheme
(R)-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-(1-methylethyl)propanoic acid
172900-71-9

(R)-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-(1-methylethyl)propanoic acid

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 12 steps
1: 95 percent / LAH / tetrahydrofuran
2: 97 percent / PPh3; NBS / CH2Cl2
3: 68 percent / n-BuLi
4: HCl / acetonitrile
5: Et3N
6: NaBH4 / ethanol
7: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
8: Mg
9: 23 percent / H2 / Pd(OH)2/C
10: 38 percent / TPAP; NMMO
11: 65 percent / 2-hydroxypyridine; Et3N
12: TMSCl; phenol / CH2Cl2
View Scheme
Multi-step reaction with 8 steps
1: 90 percent / NaBH4; I2 / 96 h / 20 °C
2: 70 percent / SOCl2; pyridine
3: Mg; BrCH2CH2Br / tetrahydrofuran / 20 °C
4: H2 / [Ru2Cl4((S)-BINAP)]NEt3 / methanol / 40 h / 40 °C / 37503 Torr
5: NEt3 / CH2Cl2
6: 85 percent / NaN3; 15-crown-6; DMPU
7: 59 percent / 2-OH-pyridine; NEt3
8: H2; aq. HCl / Pd/C / methanol
View Scheme
Multi-step reaction with 9 steps
1.1: sodium tetrahydroborate / tetrahydrofuran / 1 h / 0 - 5 °C / Inert atmosphere
1.2: 5.75 h / 0 - 30 °C
2.1: N-chloro-succinimide; triphenylphosphine / dichloromethane / 5.5 h / -40 - 30 °C
3.1: magnesium; ethylene dibromide / tetrahydrofuran / 4.17 h / 63 - 68 °C / Inert atmosphere
3.2: 12.5 h / 0 - 5 °C
4.1: water; lithium hydroxide / tetrahydrofuran; methanol / 26 h / 65 - 70 °C
4.2: 0.5 h / 0 - 5 °C
5.1: hydrogenchloride / 1,1-dichloroethane; water / 0 - 5 °C / pH 2.5
5.2: 14.25 h / 0 - 30 °C
6.1: N-Bromosuccinimide; phosphoric acid / water; tetrahydrofuran / 1.25 h / 0 - 5 °C
7.1: sodium azide / ethylene glycol / 20 h / 80 - 85 °C
8.1: triethylamine; 2-hydroxypyridin / 16 h / 85 - 90 °C
9.1: hydrogen; ethanolamine / palladium 10% on activated carbon / isopropyl alcohol / 3 h
View Scheme
(2R)-3-methyl-2-[(phenylmethoxy)methyl]butan-1-ol
365541-75-9

(2R)-3-methyl-2-[(phenylmethoxy)methyl]butan-1-ol

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1: 61 percent / PPh3; NBS / CH2Cl2
2: Mg
3: 23 percent / H2 / Pd(OH)2/C
4: 38 percent / TPAP; NMMO
5: 65 percent / 2-hydroxypyridine; Et3N
6: TMSCl; phenol / CH2Cl2
View Scheme
(4R)-3-{(2S)-3-methyl-1-oxo-2-[(phenylmethoxy)methyl]butyl}-4-(phenylmethyl)oxazolidin-2-one
365541-74-8

(4R)-3-{(2S)-3-methyl-1-oxo-2-[(phenylmethoxy)methyl]butyl}-4-(phenylmethyl)oxazolidin-2-one

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1: 82 percent / LiOH; H2O2
2: 86 percent / LAH / tetrahydrofuran
3: 61 percent / PPh3; NBS / CH2Cl2
4: Mg
5: 23 percent / H2 / Pd(OH)2/C
6: 38 percent / TPAP; NMMO
7: 65 percent / 2-hydroxypyridine; Et3N
8: TMSCl; phenol / CH2Cl2
View Scheme
(2S)-(benzyloxymethyl)-3-methyl-butyl bromide
172901-00-7

(2S)-(benzyloxymethyl)-3-methyl-butyl bromide

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: Mg
2: 23 percent / H2 / Pd(OH)2/C
3: 38 percent / TPAP; NMMO
4: 65 percent / 2-hydroxypyridine; Et3N
5: TMSCl; phenol / CH2Cl2
View Scheme
(2S)-3-methyl-2-[(phenylmethoxy)methyl]butanoic acid
656241-26-8

(2S)-3-methyl-2-[(phenylmethoxy)methyl]butanoic acid

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1: 86 percent / LAH / tetrahydrofuran
2: 61 percent / PPh3; NBS / CH2Cl2
3: Mg
4: 23 percent / H2 / Pd(OH)2/C
5: 38 percent / TPAP; NMMO
6: 65 percent / 2-hydroxypyridine; Et3N
7: TMSCl; phenol / CH2Cl2
View Scheme
4-(bromomethyl)-1-methoxy-2-(3-methoxypropoxy)-benzene
172900-73-1

4-(bromomethyl)-1-methoxy-2-(3-methoxypropoxy)-benzene

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 14 steps
1: 76 percent / LiHMDS / tetrahydrofuran
2: 81 percent / LiOH; H2O2
3: 95 percent / LAH / tetrahydrofuran
4: 97 percent / PPh3; NBS / CH2Cl2
5: 68 percent / n-BuLi
6: HCl / acetonitrile
7: Et3N
8: NaBH4 / ethanol
9: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
10: Mg
11: 23 percent / H2 / Pd(OH)2/C
12: 38 percent / TPAP; NMMO
13: 65 percent / 2-hydroxypyridine; Et3N
14: TMSCl; phenol / CH2Cl2
View Scheme
Multi-step reaction with 11 steps
1.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / -70 °C / Inert atmosphere
1.2: -70 - 5 °C
2.1: dihydrogen peroxide; lithium hydroxide monohydrate / water; tetrahydrofuran / 0 - 30 °C
3.1: sodium tetrahydroborate / tetrahydrofuran / 1 h / 0 - 5 °C / Inert atmosphere
3.2: 5.75 h / 0 - 30 °C
4.1: N-chloro-succinimide; triphenylphosphine / dichloromethane / 5.5 h / -40 - 30 °C
5.1: magnesium; ethylene dibromide / tetrahydrofuran / 4.17 h / 63 - 68 °C / Inert atmosphere
5.2: 12.5 h / 0 - 5 °C
6.1: water; lithium hydroxide / tetrahydrofuran; methanol / 26 h / 65 - 70 °C
6.2: 0.5 h / 0 - 5 °C
7.1: hydrogenchloride / 1,1-dichloroethane; water / 0 - 5 °C / pH 2.5
7.2: 14.25 h / 0 - 30 °C
8.1: N-Bromosuccinimide; phosphoric acid / water; tetrahydrofuran / 1.25 h / 0 - 5 °C
9.1: sodium azide / ethylene glycol / 20 h / 80 - 85 °C
10.1: triethylamine; 2-hydroxypyridin / 16 h / 85 - 90 °C
11.1: hydrogen; ethanolamine / palladium 10% on activated carbon / isopropyl alcohol / 3 h
View Scheme
Multi-step reaction with 10 steps
1.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / -70 °C / Inert atmosphere
1.2: -70 - 5 °C
2.1: sodium tetrahydroborate / tetrahydrofuran / 0 - 15 °C
2.2: 11 h / 60 - 65 °C
3.1: N-chloro-succinimide; triphenylphosphine / dichloromethane / 5.5 h / -40 - 30 °C
4.1: magnesium; ethylene dibromide / tetrahydrofuran / 4.17 h / 63 - 68 °C / Inert atmosphere
4.2: 12.5 h / 0 - 5 °C
5.1: water; lithium hydroxide / tetrahydrofuran; methanol / 26 h / 65 - 70 °C
5.2: 0.5 h / 0 - 5 °C
6.1: hydrogenchloride / 1,1-dichloroethane; water / 0 - 5 °C / pH 2.5
6.2: 14.25 h / 0 - 30 °C
7.1: N-Bromosuccinimide; phosphoric acid / water; tetrahydrofuran / 1.25 h / 0 - 5 °C
8.1: sodium azide / ethylene glycol / 20 h / 80 - 85 °C
9.1: triethylamine; 2-hydroxypyridin / 16 h / 85 - 90 °C
10.1: hydrogen; ethanolamine / palladium 10% on activated carbon / isopropyl alcohol / 3 h
View Scheme
[4-methoxy-3-(3-methoxypropoxy)-phenyl]methanol
172900-74-2

[4-methoxy-3-(3-methoxypropoxy)-phenyl]methanol

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 15 steps
1: PBr3 / CH2Cl2
2: 76 percent / LiHMDS / tetrahydrofuran
3: 81 percent / LiOH; H2O2
4: 95 percent / LAH / tetrahydrofuran
5: 97 percent / PPh3; NBS / CH2Cl2
6: 68 percent / n-BuLi
7: HCl / acetonitrile
8: Et3N
9: NaBH4 / ethanol
10: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
11: Mg
12: 23 percent / H2 / Pd(OH)2/C
13: 38 percent / TPAP; NMMO
14: 65 percent / 2-hydroxypyridine; Et3N
15: TMSCl; phenol / CH2Cl2
View Scheme
Multi-step reaction with 12 steps
1.1: phosphorus tribromide / dichloromethane / 2.17 h / 0 - 5 °C
2.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / -70 °C / Inert atmosphere
2.2: -70 - 5 °C
3.1: dihydrogen peroxide; lithium hydroxide monohydrate / water; tetrahydrofuran / 0 - 30 °C
4.1: sodium tetrahydroborate / tetrahydrofuran / 1 h / 0 - 5 °C / Inert atmosphere
4.2: 5.75 h / 0 - 30 °C
5.1: N-chloro-succinimide; triphenylphosphine / dichloromethane / 5.5 h / -40 - 30 °C
6.1: magnesium; ethylene dibromide / tetrahydrofuran / 4.17 h / 63 - 68 °C / Inert atmosphere
6.2: 12.5 h / 0 - 5 °C
7.1: water; lithium hydroxide / tetrahydrofuran; methanol / 26 h / 65 - 70 °C
7.2: 0.5 h / 0 - 5 °C
8.1: hydrogenchloride / 1,1-dichloroethane; water / 0 - 5 °C / pH 2.5
8.2: 14.25 h / 0 - 30 °C
9.1: N-Bromosuccinimide; phosphoric acid / water; tetrahydrofuran / 1.25 h / 0 - 5 °C
10.1: sodium azide / ethylene glycol / 20 h / 80 - 85 °C
11.1: triethylamine; 2-hydroxypyridin / 16 h / 85 - 90 °C
12.1: hydrogen; ethanolamine / palladium 10% on activated carbon / isopropyl alcohol / 3 h
View Scheme
Multi-step reaction with 10 steps
1.1: phosphorus tribromide / dichloromethane / 2.17 h / 0 - 5 °C
2.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / -70 °C / Inert atmosphere
2.2: -70 - 5 °C
3.1: dihydrogen peroxide; lithium hydroxide monohydrate / water; tetrahydrofuran / 0 - 30 °C
4.1: sodium tetrahydroborate / tetrahydrofuran / 1 h / 0 - 5 °C / Inert atmosphere
4.2: 5.75 h / 0 - 30 °C
5.1: N-chloro-succinimide; triphenylphosphine / dichloromethane / 5.5 h / -40 - 30 °C
6.1: magnesium; ethylene dibromide / tetrahydrofuran / 4.17 h / 63 - 68 °C / Inert atmosphere
6.2: 12.5 h / 0 - 5 °C
7.1: water; lithium hydroxide / tetrahydrofuran; methanol / 26 h / 65 - 70 °C
7.2: 0.5 h / 0 - 5 °C
8.1: hydrogenchloride / 1,1-dichloroethane; water / 0 - 5 °C / pH 2.5
8.2: 14.25 h / 0 - 30 °C
9.1: N-Bromosuccinimide; phosphoric acid / water; tetrahydrofuran / 1.25 h / 0 - 5 °C
10.1: 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone / 4 h / 75 - 80 °C
10.2: 15 h / 85 - 90 °C
10.3: 3 h
View Scheme
(R)-4-(2-(bromomethyl)-3-methylbutyl)-1-methoxy-2-(3-methoxypropoxy)benzene
172900-69-5

(R)-4-(2-(bromomethyl)-3-methylbutyl)-1-methoxy-2-(3-methoxypropoxy)benzene

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 10 steps
1: 68 percent / n-BuLi
2: HCl / acetonitrile
3: Et3N
4: NaBH4 / ethanol
5: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
6: Mg
7: 23 percent / H2 / Pd(OH)2/C
8: 38 percent / TPAP; NMMO
9: 65 percent / 2-hydroxypyridine; Et3N
10: TMSCl; phenol / CH2Cl2
View Scheme
(2S,4S)-2-Amino-4-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-5-methyl-hexanoic acid ethyl ester
172900-99-1

(2S,4S)-2-Amino-4-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-5-methyl-hexanoic acid ethyl ester

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1: Et3N
2: NaBH4 / ethanol
3: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
4: Mg
5: 23 percent / H2 / Pd(OH)2/C
6: 38 percent / TPAP; NMMO
7: 65 percent / 2-hydroxypyridine; Et3N
8: TMSCl; phenol / CH2Cl2
View Scheme
(2S,4S)-2-{[(tert-butoxy)carbonyl]amino}-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexan-1-ol
172900-82-2

(2S,4S)-2-{[(tert-butoxy)carbonyl]amino}-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexan-1-ol

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
2: Mg
3: 23 percent / H2 / Pd(OH)2/C
4: 38 percent / TPAP; NMMO
5: 65 percent / 2-hydroxypyridine; Et3N
6: TMSCl; phenol / CH2Cl2
View Scheme
ethyl (2S,4S)-2-{[(tert-butoxy)carbonyl]amino}-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexanoate
172900-76-4

ethyl (2S,4S)-2-{[(tert-butoxy)carbonyl]amino}-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexanoate

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1: NaBH4 / ethanol
2: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2
3: Mg
4: 23 percent / H2 / Pd(OH)2/C
5: 38 percent / TPAP; NMMO
6: 65 percent / 2-hydroxypyridine; Et3N
7: TMSCl; phenol / CH2Cl2
View Scheme
(2E)-but-2-enedioic acid
110-17-8

(2E)-but-2-enedioic acid

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S,4S,5S,7S)-N-(2-carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxypropoxy)phenyl]octanamide hemifumarate

(2S,4S,5S,7S)-N-(2-carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxypropoxy)phenyl]octanamide hemifumarate

Conditions
ConditionsYield
In ethanol; ethyl acetate93.6%
Stage #1: (2E)-but-2-enedioic acid; (2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide In ethanol; acetonitrile at 20 - 50℃; for 0.333333h;
Stage #2: In ethanol; acetonitrile at 17 - 37℃; for 12.6667h; Product distribution / selectivity; aliskiren modification A;
In methanol at 40 - 45℃; Temperature; Solvent; Concentration;3.8 g
oxalic acid
144-62-7

oxalic acid

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide hemioxalate

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide hemioxalate

Conditions
ConditionsYield
In water for 0.333333h;93.36%
succinic acid
110-15-6

succinic acid

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide hemisuccinate

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide hemisuccinate

Conditions
ConditionsYield
In water for 0.25h;92.6%
citric acid
77-92-9

citric acid

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide citrate

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide citrate

Conditions
ConditionsYield
In water for 0.5h; Product distribution / selectivity;92.37%
(2E)-but-2-enedioic acid
110-17-8

(2E)-but-2-enedioic acid

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S,4S,5S,7S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxypropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-(2-propan-2-yl)nonanamide hemifumarate
173334-58-2

(2S,4S,5S,7S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxypropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-(2-propan-2-yl)nonanamide hemifumarate

Conditions
ConditionsYield
In methanol Solvent; Concentration; Time; Temperature;81.5%
In methanol at 35℃; for 1h; Product distribution / selectivity;74.25%
In ethanol at 20℃; Product distribution / selectivity;
L-Tartaric acid
87-69-4

L-Tartaric acid

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide hemi(L-tartrate)

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide hemi(L-tartrate)

Conditions
ConditionsYield
In ethanol; acetonitrile at 20℃; for 0.0833333h; Product distribution / selectivity;72.85%
(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide phosphate
1327153-75-2

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide phosphate

Conditions
ConditionsYield
With phosphoric acid In water at 20℃; for 0.5h; Product distribution / selectivity;70.8%
acetic acid
64-19-7

acetic acid

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide acetate
1327153-77-4

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide acetate

Conditions
ConditionsYield
In water for 0.5h;65%
(S)-Malic acid
97-67-6

(S)-Malic acid

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide L-malate
1327153-72-9

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide L-malate

Conditions
ConditionsYield
In water for 0.5h; Product distribution / selectivity;63.3%
In ethanol; dichloromethane at 20℃; for 24h;
pentafluorophenol 4-nitroxybutyrate
838878-70-9

pentafluorophenol 4-nitroxybutyrate

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S,4S,5S,7S)-5-[4-(nitrooxy)butanoyl]amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propopxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S,4S,5S,7S)-5-[4-(nitrooxy)butanoyl]amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propopxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
With dmap; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 4h;50%
4-(nitrooxy)butyl 4-nitrophenyl carbonate
935472-60-9

4-(nitrooxy)butyl 4-nitrophenyl carbonate

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S,4S,5S,7S)-5-[[[4-(nitrooxy)butyl]oxy]carbonyl]amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propopxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S,4S,5S,7S)-5-[[[4-(nitrooxy)butyl]oxy]carbonyl]amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propopxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
With dmap; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 4h;50%
pentafluorophenol 4-nitroxybutyrate
838878-70-9

pentafluorophenol 4-nitroxybutyrate

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S,4S,5S,7S)-5-[4-(nitrooxy)butanoyl]amino-4-[4-(nitrooxy)butanoyl]oxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propopxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S,4S,5S,7S)-5-[4-(nitrooxy)butanoyl]amino-4-[4-(nitrooxy)butanoyl]oxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propopxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
With dmap; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 4h;45%
[4-(nitrooxy)methyl]benzoic acid pentafluorophenyl ester
874446-96-5

[4-(nitrooxy)methyl]benzoic acid pentafluorophenyl ester

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S,4S,5S,7S)-5-[4-[(nitrooxy)methyl]benzoyl]amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propopxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

(2S,4S,5S,7S)-5-[4-[(nitrooxy)methyl]benzoyl]amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propopxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Conditions
ConditionsYield
With dmap; scandium tris(trifluoromethanesulfonate) In N,N-dimethyl-formamide at 0 - 20℃; for 4h;30%
(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide
173334-57-1

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

2(S),4(S),5(S),7(S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide, hydrogen sulfate salt of

2(S),4(S),5(S),7(S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide, hydrogen sulfate salt of

Conditions
ConditionsYield
With sulfuric acid In water; acetonitrile at 0 - 5℃; for 10 - 48h;n/a
With sulfuric acid In water; acetonitrile at 0 - 5℃; for 11 - 49h;n/a

173334-57-1Downstream Products

173334-57-1Relevant articles and documents

End-to-end continuous manufacturing of pharmaceuticals: Integrated synthesis, purification, and final dosage formation

Mascia, Salvatore,Heider, Patrick L.,Zhang, Haitao,Lakerveld, Richard,Benyahia, Brahim,Barton, Paul I.,Braatz, Richard D.,Cooney, Charles L.,Evans, James M. B.,Jamison, Timothy F.,Jensen, Klavs F.,Myerson, Allan S.,Trout, Bernhardt L.

, p. 12359 - 12363 (2013)

A series of tubes: The continuous manufacture of a finished drug product starting from chemical intermediates is reported. The continuous pilot-scale plant used a novel route that incorporated many advantages of continuous-flow processes to produce active pharmaceutical ingredients and the drug product in one integrated system. Copyright

Development of a multi-step synthesis and workup sequence for an integrated, continuous manufacturing process of a pharmaceutical

Heider, Patrick L.,Born, Stephen C.,Basak, Soubir,Benyahia, Brahim,Lakerveld, Richard,Zhang, Haitao,Hogan, Rachael,Buchbinder, Louis,Wolfe, Aaron,Mascia, Salvatore,Evans, James M. B.,Jamison, Timothy F.,Jensen, Klavs F.

, p. 402 - 409 (2014)

The development and operation of the synthesis and workup steps of a fully integrated, continuous manufacturing plant for synthesizing aliskiren, a small molecule pharmaceutical, are presented. The plant started with advanced intermediates, two synthetic steps away from the final active pharmaceutical ingredient, and ended with finished tablets. The entire process was run on several occasions, with the data presented herein corresponding to a 240 h run at a nominal throughput of 41 g h-1 of aliskiren. The first reaction was performed solvent-free in a molten condition at a high temperature, achieving high yields (90%) and avoiding solid handling and a long residence time (due to higher concentrations compared to dilute conditions when run at lower temperatures in a solvent). The resulting stream was worked-up inline using liquid-liquid extraction with membrane-based separators that were scaled-up from microfluidic designs. The second reaction involved a Boc deprotection, using aqueous HCl that was rapidly quenched with aqueous NaOH using an inline pH measurement to control NaOH addition. The reaction maintained high yields (90-95%) under closed-loop control despite process disturbances.

Preparation method of aliskiren

-

, (2017/02/02)

The invention discloses a preparation method of aliskiren. Aliskiren is prepared from (R)-t-butylsulfenamide and a compound VIII. The chiral induction effect of the (R)-t-butylsulfenamide is used to construct a required second chiral center and solve the problem of column chromatographic separation needed in the construction of a second chiral center, a third chiral center and a fourth chiral center. The preparation method of aliskiren has the advantages of simple operation, high yield, low cost, high device utilization rate, and suitableness for industrial production.

PROCESS FOR THE PREPARATION OF ALISKIREN

-

, (2014/09/29)

The present invention provides a novel process and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially renin inhibitors, such as Aliskiren, or a salt thereof, preferably Aliskiren hemifumarate.

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