Triethylamine → HCID 118276695, compound

HRID 1053670Notes

Reaction equation

HRID 1053670 reaction equation
[C:1]([O:5][C:6](=[O:27])[CH2:7][C@H:8]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:9][C:10]1[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=1[C:12]([OH:14])=O)([CH3:4])([CH3:3])[CH3:2].ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1.Cl.[Cl:52][CH2:53][CH2:54][NH:55][CH2:56][CH2:57][Cl:58].C(N(CC)CC)C>C(#N)C>[Cl:52][CH2:53][CH2:54][N:55]([CH2:56][CH2:57][Cl:58])[C:12]([C:11]1[CH:15]=[CH:16][CH:17]=[CH:18][C:10]=1[CH2:9][C@@H:8]([NH:19][C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:27])=[O:14]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 118276663HCID 118276663, compound

Product 1

HCID 118276695HCID 118276695, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Adapting a literature known protocol (Levi and Weed, U.S. Pat. No. 3,235,594), to a reaction mixture of 2-[(2R)-4-tert-butoxy-2-(tert-butoxycarbonylamino)-4-oxo-butyl]benzoic acid (23b) (759 mg, 2.0 mmol), N-hydroxysuccinimide (NHS, HOSu) (235 mg, 2.2 mmol) in anhydrous acetonitrile (MeCN) (10 mL) is added solid dicyclohexylcarbodiimide (DCC) (433 mg, 2.1 mmol) in small portions at about room temperature. The reaction mixture is stirred for about 12 hours and the precipitated dicyclohexylurea side product is filtered off using a Büchner funnel. The filtrate is treated with commercial di-(2-chloroethyl)amine hydrochloride (2-chloro-N-(2-chloroethyl)ethanamine hydrochloride; HN(CH2—CH2—Cl)2.HCl) (393 mg, 2.2 mmol) followed by neat triethylamine (Et3N, TEA) (321 μL, 233 mg, 2.3 mmol). The reaction mixture is stirred for about 12 hours at room temperature. The reaction is followed by TLC and/or LC/MS to completion. Acidic aqueous work-up and purification by silica gel column chromatography furnish the title compound tert-butyl(3R)-4-[2-[bis(2-chloroethyl)carbamoyl]phenyl]-3-(tert-butoxycarbonylamino)butanoate (23c).

Workup

  1. filtrationthe precipitated dicyclohexylurea side product is filtered off
  2. stirringThe reaction mixture is stirred for about 12 hours at room temperature
  3. customAcidic aqueous work-up and purification by silica gel column chromatography

Sources & evidence

ORD record
ord-0828894962f14249b233cfea0feba800
Source dataset
uspto-grants-2016_07
Patent number
US09394237B2

Reaction notes

Loading…