118753-70-1

Basic information

• Product Name: N-Boc-N,N-bis(2-chloroethyl)amine
• Synonyms: TERT-BUTYL BIS(2-CHLOROETHYL)CARBAMATE;bis(2-chloroethyl)-carbamic acid tert-butyl ester;N-Boc-N,N-bis(2-chloroethyl)amine ,95%;Bis(2-chloroethyl)-N-(tert-butoxycarbonyl)aMine;Bis(2-chloroethyl)-tert-butoxycarbonylaMine;CarbaMic acid, bis(2-chloroethyl)-, 1,1-diMethylethyl ester (9CI);Carbamic acid,N,N-bis(2-chloroethyl)-, 1,1-dimethylethyl ester;N-Boc-Bis(2-chloroethyl) amine
• CAS NO: 118753-70-1
• Molecular Formula: C₉H₁₇Cl₂NO₂
• Molecular Weight: 242.14
• Product Categories: pharmacetical
• Mol File: 118753-70-1.mol
• Article Data: 58

Chemical Properties

• Boiling Point: 290.662 °C at 760 mmHg
• Flash Point: 129.588 °C
• Appearance: White to off-white powder
• Density: 1.149 g/cm³
• Vapor Pressure: 0.002mmHg at 25°C
• Refractive Index: 1.471
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• PKA: -1.73±0.70(Predicted)
• CAS DataBase Reference: N-Boc-N,N-bis(2-chloroethyl)amine(CAS DataBase Reference)
• NIST Chemistry Reference: N-Boc-N,N-bis(2-chloroethyl)amine(118753-70-1)
• EPA Substance Registry System: N-Boc-N,N-bis(2-chloroethyl)amine(118753-70-1)

Safety Data

• Hazardous Substances Data: 118753-70-1(Hazardous Substances Data)

Usage

General Description

N-Boc-N,N-bis(2-chloroethyl)amine, also known as bis(2-chloroethyl)carbamic acid tert-butyl ester, is a chemical compound used in the synthesis of pharmaceuticals. It is a bifunctional alkylating agent that has been studied for its potential use in cancer treatment. N-Boc-N,N-bis(2-chloroethyl)amine contains two chloroethyl groups, which are known for their ability to form covalent bonds with DNA, leading to DNA cross-linking and ultimately cell death. Due to its potential cytotoxic effects, N-Boc-N,N-bis(2-chloroethyl)amine is of interest to researchers and pharmaceutical companies for its potential use in cancer chemotherapy. However, it is also important to note that this compound is highly toxic and requires careful handling and proper safety measures when used in a laboratory setting.

InChI:InChI=1/C9H17Cl2NO2/c1-9(2,3)14-8(13)12(6-4-10)7-5-11/h4-7H2,1-3H3

Synthetic route

di-tert-butyl dicarbonate (24424-99-5) + bis-(2-chloroethyl)amine hydrochloride (821-48-7) → N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1)

Conditions	Yield
With triethylamine	100%
In dichloromethane	100%
With sodium hydroxide In dichloromethane at 20℃; for 18.5h;	100%

di-tert-butyl dicarbonate (24424-99-5) + N,N-bis(chloro-2-ethyl)amine (334-22-5) → N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	49%
With triethylamine In dichloromethane at 0 - 20℃;	49%
With N-ethyl-N,N-diisopropylamine In dichloromethane

di-tert-butyl dicarbonate (24424-99-5) + bis-(2-chloroethyl)amine hydrochloride (821-48-7) → 4-aminomethyl-4-(4-iodo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (473735-52-3) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1)

Conditions	Yield
With triethanolamine In dichloromethane	A 42% B n/a

di-tert-butyl dicarbonate (24424-99-5) + N,N-bis(chloro-2-ethyl)amine (334-22-5) → N-(2,2'-bischloro)-diethyl-N-(1,1-dimethylethoxy)carbonyl amine + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane
With N-ethyl-N,N-diisopropylamine In dichloromethane
With N-ethyl-N,N-diisopropylamine In dichloromethane

bis-(2-chloroethyl)amine hydrochloride (821-48-7) → N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1)

N,N-bis(chloro-2-ethyl)amine (334-22-5) → N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1)

2-(4-chloro-2-fluoro-phenyl)acetonitrile (75279-53-7) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → 1,1-dimethylethyl 4-(4-chloro-2-fluorophenyl)-4-cyano-1-piperidinecarboxylate (1093956-69-4)

Conditions	Yield
With sodium hydroxide; methyl tributylammonium chloride In water; toluene at 40℃; for 14h; Product distribution / selectivity;	100%
Stage #1: 2-(4-chloro-2-fluoro-phenyl)acetonitrile With sodium hydride In dimethyl sulfoxide at 20℃; for 1h; Stage #2: N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine In dimethyl sulfoxide at 20℃; for 3h;	38%
Stage #1: 2-(4-chloro-2-fluoro-phenyl)acetonitrile With sodium hydride In dimethyl sulfoxide at 23℃; for 0.166667h; Stage #2: N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine In dimethyl sulfoxide at 85℃; for 1.5h;	38%
Stage #1: 2-(4-chloro-2-fluoro-phenyl)acetonitrile With sodium hydride In dimethyl sulfoxide at 23℃; for 0.166667h; Stage #2: N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine In dimethyl sulfoxide at 85℃; for 1.5h;	38%
With sodium hydride In dimethyl sulfoxide

N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → 1-t-Butoxycarbonylpiperazine (57260-71-6)

Conditions	Yield
With ammonium hydroxide at 60℃; for 5.5h; Time;	94.3%

4-amino-phenol (123-30-8) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → tert-butyl 4-(4-hydroxyphenyl)piperazine-1-carboxylate (158985-25-2)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 20h;	93%

N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) + potassium thioacetate (10387-40-3) → N-tert-butoxycarbonyl bis(2-thioacetoxyethyl)amine (321658-86-0)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 48h;	89.8%
In N,N-dimethyl-formamide at 20℃; for 72h;	82%
In N,N-dimethyl-formamide at 20℃; for 48h;	35%

(2-benzyloxyphenyl)acetonitrile (92552-22-2) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → C19H20N2O

Conditions	Yield
Stage #1: (2-benzyloxyphenyl)acetonitrile With sodium hydride In Pionier 2076; N,N-dimethyl-formamide at 0 - 23℃; for 0.166667h; Stage #2: N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine In Pionier 2076; N,N-dimethyl-formamide at 0 - 80℃; Stage #3: With ammonium chloride In Pionier 2076; water; N,N-dimethyl-formamide	74%

N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) + p-chlorobenzyl cyanide (140-53-4) → 4-(4-chloro-phenyl)-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (218451-34-4)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 60℃; Inert atmosphere;	71%
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 60℃; Inert atmosphere;	71%
With sodium hydride In N,N-dimethyl-formamide at 20 - 65℃;	70%

3-chloro-benzeneacetonitrile (1529-41-5) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → tert-butyl 4-(3-chlorophenyl)-4-cyanopiperidine-1-carboxylate (553631-33-7)

Conditions	Yield
With 18-crown-6 ether; potassium tert-butylate In toluene for 12h; Reflux;	70%
With sodium hydride In tetrahydrofuran; dimethyl sulfoxide at 20 - 60℃;

pyridin-4-yl-acetic acid ethyl ester (54401-85-3) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → 1-tert-butyl 4-ethyl 4-(pyridin-4-yl)piperidine-1,4-dicarboxylate (954125-18-9)

Conditions	Yield
With 18-crown-6 ether; sodium hydride In N,N-dimethyl-formamide at 25℃; for 4h;	67%

2-(2,6-difluoro-4-methoxyphenyl)acetonitrile (886499-03-2) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → 1-(tert-butyloxycarbonyl)-4-(2,6-difluoro-4-methoxyphenyl)piperidine-4-carbonitrile

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; paraffin oil at 0 - 80℃; for 3h;	66%
With sodium hydride In N,N-dimethyl-formamide at 80℃; for 3h;	881.4 mg

N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) + 1-indene (95-13-6) → 1'-(tert-butyloxycarbonyl)spiro<1H-indene-1,4'-piperidine> (137419-24-0)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at 0℃;	65%
With lithium hexamethyldisilazane; hydrazine In tetrahydrofuran at 2℃; for 2.5h; Cooling with ice;	58%
Stage #1: 1-indene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 1h; Stage #2: N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine In tetrahydrofuran at 0 - 20℃; for 2.5h;	57%

C26H36O4Si (1197860-92-6) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → C35H51NO6Si (1197860-97-1)

Conditions	Yield
Stage #1: C26H36O4Si With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Stage #2: N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine In tetrahydrofuran at -78 - 0℃; for 8h; regioselective reaction;	65%

C16H21NO3 (1292306-61-6) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → C25H36N2O5 (1292306-62-7)

Conditions	Yield
With sodium hydride In Pionier 2076; N,N-dimethyl-formamide at 0 - 75℃; for 5h;	65%

2,6-bis(mercaptomethyl)pyridine (13671-28-8) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → N-t-butoxycarbonyl 2,8-dithia-5-aza-2,6-pyridinophane (771500-96-0)

Conditions	Yield
Stage #1: 2,6-bis(mercaptomethyl)pyridine; N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine With CsCO3 In N,N-dimethyl-formamide at 55℃; for 24h; Stage #2: In N,N-dimethyl-formamide at 20℃; for 20h; Further stages.;	64%

(3-bromophenyl)acetonitrile (31938-07-5) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → tert-butyl 4-(3-bromophenyl)-4-cyanopiperidine-1-carboxylate (849928-28-5)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 60℃; for 17h;	63%
With sodium hydride In N,N-dimethyl-formamide at 0 - 60℃; for 3h; Inert atmosphere;

2-(2-chloropyridin-3-yl)acetonitrile (101012-32-2) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → 2-chloro-4'-cyano-3',4',5',6'-tetrahydro-2'H-[3,4']-bipyridinyl-1'-carboxylic acid tert-butyl ester (1315335-16-0)

Conditions	Yield
Stage #1: 2-(2-chloropyridin-3-yl)acetonitrile With sodium hydride In dimethyl sulfoxide at 20℃; for 1h; Stage #2: N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine In dimethyl sulfoxide at 70℃; for 2h;	61%
Stage #1: 2-(2-chloropyridin-3-yl)acetonitrile With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.166667h; Stage #2: N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine In N,N-dimethyl-formamide at 0 - 20℃; for 5.16h;	16.5 g

2,7-dibromo-9H-fluorene (16433-88-8) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → tert-butyl 2,7-dibromospiro[fluorene-9,4'-piperidine]-1'-carboxylate (1616113-98-4)

Conditions	Yield
Stage #1: 2,7-dibromo-9H-fluorene With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 0.5h; Stage #2: N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine In tetrahydrofuran; mineral oil at 0℃; for 4h; Reflux;	61%

p-methoxybenzylnitrile (104-47-2) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → tert-butyl 4-cyano-4-(4-methoxyphenyl)piperidine-1-carboxylate (553631-38-2)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 60℃; for 17h;	61%

4-fluorophenylacetonitrile (459-22-3) + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → 4-(4-fluorophenyl)-tert-butoxycarbonylpiperidine-4-carbonitrile (256951-79-8)

Conditions	Yield
Stage #1: 4-fluorophenylacetonitrile With sodium hydride In dimethyl sulfoxide at 20℃; for 1.5h; Stage #2: N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine In dimethyl sulfoxide at 20℃; for 2h;	60%
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 60℃; for 16h;	58%
With sodium hydride In N,N-dimethyl-formamide at 0 - 60℃; for 24h;	54%

2-(2-(benzyloxy)-5-bromophenyl)acetonitrile + N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine (118753-70-1) → 4-(2-benzyloxy-5-bromophenyl)-4-cyanopiperidine-1-carboxylic acid tert-butyl ester (1295645-05-4)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 60℃; for 18h;	60%

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 821-48-7 bis-(2-chloroethyl)amine hydrochloride 
• 334-22-5 N,N-bis(chloro-2-ethyl)amine 

Downstream Products

• 634465-43-3 tert-butyl 4-cyano-4-[3-(trifluoromethyl)phenyl]-1-piperidine carboxylate 
• 553631-33-7 tert-butyl 4-(3-chlorophenyl)-4-cyanopiperidine-1-carboxylate 
• 216311-18-1 4-cyano-4-(2,4-dichlorophenyl)-piperidine-1-carboxylic acid tert-butyl ester 
• 1093956-69-4 1,1-dimethylethyl 4-(4-chloro-2-fluorophenyl)-4-cyano-1-piperidinecarboxylate 
• 1150315-87-9 1,1-dimethylethyl 4-cyano-4-(2-fluoro-4-methylphenyl)-1-piperidinecarboxylate 
• 1197860-97-1 C₃₅H₅₁NO₆Si 
• 752234-64-3 tert-butyl 5-methoxy-2-oxo-1,2-dihydro-1'H-spiro[indole-3,4'-piperidine]-1'-carboxylate 
• 866028-06-0 tert-butyl 5-fluoro-2-oxospiro[indoline-3,4'-piperidine]-1'-carboxylate 
• 857532-26-4 4-(4-chloro-phenyl)-3,4,5,6-tetrahydro-2H-[4,4']bipyridinyl-1-carboxylic acid tert-butyl ester 
• 1254784-67-2 C₂₂H₃₃N₃O₆ 
• 952153-85-4 C₂₅H₃₁N₃O₆ 
• 1035346-57-6 tert-butyl 4-(3-bromo-5-fluorophenyl)-4-cyanopiperidine-1-carboxylate 
• 252882-60-3 tert-butyl 2-oxo-1,2-dihydro-1'H-spiro[indole-3,4-piperidine]-1'-carboxylate 
• 118753-66-5 4-Amino-piperazine-1-carboxylic acid tert-butyl ester 

Relevant articles and documents

A convenient synthesis of 1′-H-spiro-(indoline-3,4′-piperidine) and its derivatives

A simple synthetic route has been developed to prepare 1′-H- spiro(indoline-3,4′-piperidine) (1d). Dialkylation of 2- fluorophenylacetonitrile with N-(tert-butyloxycarbonyl)-bis(2-chloroethyl)amine (5) gave 6. Deprotection of Boc followed by cyclization resulted 1d in 67% overall yield. Selective Boc or Cbz protection of 1′-N gave 1a or 1b with 90 and 85% yield, respectively. Thus, in a five-step procedure, 1a and 1b were synthesized from commercially available reagents in over 50% overall yield. All 3 compounds (1a, 1b and 1d) can be utilized as templates to synthesize compounds for GPCR targets.

Routes to novel mono- and bis-tetrazole compounds: Synthesis, spectroscopic and structural characterization

Relatively easy-to-run synthetic routes to new mono- [1-(2-(4,5-dihydro-1H- imidazol-1-yl)ethyl)-1H-tetrazole (1) and 3-(2-(1H-tetrazol-1-yl)ethyl) oxazolidin-2-one (13)], and bis-tetrazole [N,N-bis(2-(1H-tetrazol-1-yl)ethyl) formamide (2), bis(2-(1H-tetrazol-1-yl)ethyl)amine (3), N-(2-(1H-tetrazol-1-yl) ethyl)-N-(2-(2-(1H-tetrazol-1-yl)ethylamino)ethyl)formamide (5), N 1,N2-bis(2-(1H-tetrazol-1-yl)ethyl)ethane-1,2-diamine (6), N,N′-(2,2′-azanediylbis(ethane-2,1-diyl))bis(N-(2-(1H-tetrazol-1- yl)ethyl)formamide) (8) and N1-(2-(1H-tetrazol-1-yl)ethyl)-N 2-(2-(2-(1H-tetrazol-1-yl)ethylamino)ethyl)ethane-1,2-diamine (9)] ligands have been developed. 2 (whose crystal structure is described), 3, 5, 6, 8 and 9 are of particular interest as precursors for further functionalization due to the aldehyde and secondary amine functions, while 2, 5, 8 and 13 are potential synthons for the formation of ditopic ligands for metal-organic framework construction. Unexpected instability of Boc under basic and nucleophilic conditions at high temperature followed by fragmentation of tert-butyl 2-chloroethyl(2-(2-chloroethylamino)ethyl)carbamate (14) and tert-butyl 2,2′-azanediylbis(ethane-2,1-diyl)bis(2-chloroethylcarbamate) (15) afforded 13, whose crystal structure is presented.

IRAK DEGRADERS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

6-(MORPHOLIN-4-YL)-PYRIDIN-2-YL-1H-PYRROLO[3,2-B]PYRIDINE DERIVATIVES AS M-TOR INHIBITORS

The invention relates to compounds of formula (I) wherein R1, R2, R3, R4, L and A are as defined in the description and claims, or pharmaceutically acceptable salts thereof having mTOR kinase inhibitor activity. The invention also relates to pharmaceutical compositions including a compound of formula (I) or a pharmaceutically acceptable salt thereof, and to the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in therapy, including in the treatment of a disease or condition for which an mTOR kinase inhibitor activity is indicated, and in particular the treatment of idiopathic pulmonary fibrosis.