173338-07-3

Basic information

• Product Name: CarbaMic acid, [4-[[(3-aMino-2,2-diMethyl-3-oxopropyl)aMino]carbonyl]-2-hydroxy-1-[2-[[4-Methoxy-3-(3-Methoxypropoxy)phenyl]Methyl]-3-Methylbutyl]-5-Methylhexyl]-, 1,1-diMethylethyl ester, [1S-[1R*(R*),2R*,4R*]]-
• Synonyms: CarbaMic acid, [4-[[(3-aMino-2,2-diMethyl-3-oxopropyl)aMino]carbonyl]-2-hydroxy-1-[2-[[4-Methoxy-3-(3-Methoxypropoxy)phenyl]Methyl]-3-Methylbutyl]-5-Methylhexyl]-, 1,1-diMethylethyl ester, [1S-[1R*(R*),2R*,4R*]]-;tert-butyl N-[(1S,2S,4S)-4-[(3-aMino-2,2-diMethyl-3-oxo-propyl)carbaMoyl]-2-hydroxy-1-[(2S)-2-[[4-Methoxy-3-(3-Methoxypropoxy)phenyl]Methyl]-3-Methyl-butyl]-5-Methyl-hexyl]carbaMate;tert-Butyl ((3S,5S,6S,8S)-8-((3-amino-2,2-dimethyl-3-oxopropyl)carbamoyl)-6-hydr xy-3-(4-methoxy-;N-[(1S,2S,4S)-4-[[(3-Amino-2,2-dimethyl-3-oxopropyl)amino]carbonyl]-2-hydroxy-1-[(2S)-2-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-3-methylbutyl]-5-methylhexyl]carbamic acid 1,1-dimethylethyl ester;tert-Butyl ((3S,5S,6S,8S)-8-((3-amino-2,2-dimethyl-3-oxopropyl)carbamoyl)-6-hydrxy-3-(4-methox
• CAS NO: 173338-07-3
• Molecular Formula: C₃₅H₆₁N₃O₈
• Molecular Weight: 651.87414
• Mol File: 173338-07-3.mol

Chemical Properties

• Melting Point: 141-142℃ (ethyl ether hexane )
• Boiling Point: 810.7°C at 760 mmHg
• Flash Point: 444.1°C
• Appearance: /
• Density: 1.071g/cm³
• Vapor Pressure: 8.94E-28mmHg at 25°C
• Refractive Index: 1.505
• Storage Temp.: 2-8°C
• PKA: 12.02±0.46(Predicted)
• CAS DataBase Reference: CarbaMic acid, [4-[[(3-aMino-2,2-diMethyl-3-oxopropyl)aMino]carbonyl]-2-hydroxy-1-[2-[[4-Methoxy-3-(3-Methoxypropoxy)phenyl]Methyl]-3-Methylbutyl]-5-Methylhexyl]-, 1,1-diMethylethyl ester, [1S-[1R*(R*),2R*,4R*]]-(CAS DataBase Reference)
• NIST Chemistry Reference: CarbaMic acid, [4-[[(3-aMino-2,2-diMethyl-3-oxopropyl)aMino]carbonyl]-2-hydroxy-1-[2-[[4-Methoxy-3-(3-Methoxypropoxy)phenyl]Methyl]-3-Methylbutyl]-5-Methylhexyl]-, 1,1-diMethylethyl ester, [1S-[1R*(R*),2R*,4R*]]-(173338-07-3)
• EPA Substance Registry System: CarbaMic acid, [4-[[(3-aMino-2,2-diMethyl-3-oxopropyl)aMino]carbonyl]-2-hydroxy-1-[2-[[4-Methoxy-3-(3-Methoxypropoxy)phenyl]Methyl]-3-Methylbutyl]-5-Methylhexyl]-, 1,1-diMethylethyl ester, [1S-[1R*(R*),2R*,4R*]]-(173338-07-3)

Safety Data

• Hazardous Substances Data: 173338-07-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
CarbaMic acid, [4-[[(3-aMino-2,2-diMethyl-3-oxopropyl)aMino]carbonyl]-2-hydroxy-1-[2-[[4-Methoxy-3-(3-Methoxypropoxy)phenyl]Methyl]-3-Methylbutyl]-5-Methylhexyl]-, 1,1-diMethylethyl ester, [1S-[1R(R),2R,4R]]is used as a potential drug candidate for various therapeutic applications due to its unique chemical structure and properties. Its tertiary carboxylic ester nature allows for targeted drug delivery and controlled release, enhancing its efficacy and reducing side effects. The specific application reasons and therapeutic areas for this compound may vary, but its potential in the pharmaceutical industry is promising.

InChI:InChI=1/C35H61N3O8/c1-22(2)25(17-24-13-14-29(44-11)30(18-24)45-16-12-15-43-10)19-27(38-33(42)46-34(5,6)7)28(39)20-26(23(3)4)31(40)37-21-35(8,9)32(36)41/h13-14,18,22-23,25-28,39H,12,15-17,19-21H2,1-11H3,(H2,36,41)(H,37,40)(H,38,42)/t25-,26-,27-,28-/m0/s1

Upstream product

• 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 
• 324763-51-1 aminopivalinamide 
• 666844-61-7 (2-carbamoyl-2-methylpropyl)carbamic acid benzyl ester 
• 172900-83-3 (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester 
• 866030-33-3 (2R,5S)-3,6-diethoxy-2-isopropyl-5-((S)-2-(4-methoxy-3-(3-methoxypropoxy)benzyl)-3-methylbutyl)-2,5-dihydropyrazine 
• 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 
• 172900-92-4 (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 
• 621-59-0 isovanillin 
• 7505-93-3 2-cyano-2-methylpropanamide 
• 145589-03-3 (R)-4-benzyl-3-(3-methylbutyryl)oxazolidin-2-one 
• 172900-75-3 4-methoxy-3-(3-methoxypropoxy)benzaldehyde 
• 365541-75-9 (2R)-3-methyl-2-[(phenylmethoxy)methyl]butan-1-ol 
• 365541-74-8 (4R)-3-{(2S)-3-methyl-1-oxo-2-[(phenylmethoxy)methyl]butyl}-4-(phenylmethyl)oxazolidin-2-one 
• 172900-99-1 (2S,4S)-2-Amino-4-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-5-methyl-hexanoic acid ethyl ester 

Downstream Products

• 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 
• 173399-03-6 aliskiren 
• 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 

Relevant articles and documents

Convergent Synthesis of the Renin Inhibitor Aliskiren Based on C5-C6 Disconnection and CO2H-NH2 Equivalence

A novel synthesis of the renin inhibitor aliskiren based on an unprecedented disconnection between C5 and C6 was developed, in which the C5 carbon acts as a nucleophile and the amino group is introduced by a Curtius rearrangement, which follows a simultaneous stereocontrolled generation of the C4 and C5 stereogenic centers by an asymmetric hydrogenation. Operational simplicity, step economy, and a good overall yield makes this synthesis amenable to manufacture on scale.

A stereoselective catalytic nitroaldol reaction as the key step in a strategy for the synthesis of the renin inhibitor aliskiren

Aliskiren is the first-in-class orally active direct renin inhibitor. It was approved in 2007 for the treatment of hypertension. We have designed a new strategy for the convergent synthesis of aliskiren that involves a catalytic stereoselective nitroaldol reaction as the key step. A new enantiopure nitroalkane (synthon A1), prepared in only three steps from a commercially available enantiopure 2-(arylmethyl)-3-methyl butanol derivative, was successfully used in a copper-catalysed Henry reaction to give a nitrolactone intermediate in which the correct configuration for the final product was established at all four stereocentres. Nitro-group reduction, Boc-protection of the resulting amine, aminolysis of the lactone with 3-amino-2,2-dimethylpropionamide, and finally Boc-deprotection led to the enantiopure renin inhibitor aliskiren.

PROCESS FOR PREPARING 8-ARYLOCTANOIC ACIDS

The present invention relates to a process for preparing aliskiren and, more particularly, to an improved method for synthesizing a β-amino alcohol or a lactone analog thereof via the corresponding nitro derivatives of formula (Ia) or (Ib) these intermediates being used in the preparation of aliskiren.

PROCESS FOR THE PREPARATION OF ALISKIREN

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.

Conception and evolution of stereocontrolled strategies toward functionalized 8-aryloctanoic acids related to the total synthesis of aliskiren

A detailed account is given describing the approaches used toward the total synthesis of aliskiren. In particular, ring-closing metathesis with the Hoveyda-Grubbs catalyst accelerates the formation of a 9-membered lactone from an (R)-ester. The diastereom

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

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.

PROCESS FOR THE PREPARATION OF ALISKIREN

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.

METHOD FOR PREPARING ALISKIREN AND INTERMEDIATE THEREOF

A method for preparing Aliskiren and intermediate thereof, which comprises the following steps: reacting 4-bromo-1-methoxy-2-(3-methoxypropoxy)benzene with magnesium isopropyl chloride and n-BuLi to obtain the compound of formula XXII; reacting the product of methylsulfonylation of the compound of formula XIX with anhydrous LiBr to obtain the compound of formula XXI; obtaining the intermediate of Aliskiren shown as formula XV by reacting the compound of formula XXII with the compound of formula XXI in an ether as the solvent and in the presence of a catalyst containing iron; then reacting the compound of formula XV with the compound of formula VII to obtain the compound of formula XXIII, following removing R1 from the amino group and obtaining Aliskiren shown as formula I.

METHOD FOR PREPARING ALISKIREN AND ITS INTERMEDIATES THEREOF

A method for preparing Aliskiren and intermediate thereof, which comprises the following steps: reacting 4-bromo-1-methoxy-2-(3-methoxypropoxy)benzene with magnesium isopropyl chloride and n-BuLi to obtain the compound of formula XXII; reacting the product of methylsulfonylation of the compound of formula XIX with anhydrous LiBr to obtain the compound of formula XXI; obtaining the intermediate of Aliskiren shown as formula XV by reacting the compound of formula XXII with the compound of formula XXI in an ether as the solvent and in the presence of a catalyst containing iron; then reacting the compound of formula XV with the compound of formula VII to obtain the compound of formula XXIII, following removing R1 from the amino group and obtaining Aliskiren shown as formula I.

CHEMICAL PROCESS FOR OPENING RING COMPOUNDS

It is described a process for the opening of lactone or lactam rings useful in the synthesis of pharmaceutically active compounds and the intermediates thereof, particularly Aliskiren. It has found that by selecting a type of solvent it is possible to obtain excellent yields and high optical and chemical purity of the isolated products.