Oxalyl chloride → 3-({3-[2-(tert-Butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoyl}-phenyl-amino)-propionic acid methyl ester

HRID 2268594Notes

Reaction equation

HRID 2268594 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]([O:11][C:12]([N:14]([C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1)[CH2:15][CH2:16][O:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([Cl:27])[CH:26]=1)[C:21]([OH:23])=O)=[O:13])([CH3:10])([CH3:9])[CH3:8].[CH3:34][O:35][C:36](=[O:46])[CH2:37][CH2:38][NH:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.CCN(C(C)C)C(C)C>ClCCl.CN(C1C=CN=CC=1)C.CN(C=O)C>[CH3:34][O:35][C:36](=[O:46])[CH2:37][CH2:38][N:39]([C:21](=[O:23])[C:20]1[CH:24]=[C:25]([Cl:27])[CH:26]=[C:18]([O:17][CH2:16][CH2:15][N:14]([C:12]([O:11][C:7]([CH3:10])([CH3:8])[CH3:9])=[O:13])[C:28]2[CH:29]=[CH:30][N:31]=[CH:32][CH:33]=2)[CH:19]=1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 89103N-Phenyl-beta-alanine methyl esterHCID 18348849Benzoic acid,3-chloro-5-[2-[[(1,1-dimethylethoxy)carbonyl]-4-pyridinylamino]ethoxy]-

Product 1

HCID 540560693-({3-[2-(tert-Butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoyl}-phenyl-amino)-propionic acid methyl esterYield 73.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

2M Oxalyl chloride solution in dichloromethane (1.8 ml), and DMF (0.05 ml) were added to a suspension of 3-[2-(tert-butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoic acid (1.18 g) in anhydrous dichloromethane (30 ml). The reaction was stirred at room temperature for 1 h then 3-phenylamino-propionic acid methyl ester (0.644 g), DMAP (0.036 g) and DIPEA (1.04 ml) were added. The reaction mixture was stirred at room temperature for 20 h and partitioned between ethyl acetate and 1M aqueous hydrochloric acid. The aqueous layer was removed and the organic phase washed with saturated aqueous sodium bicarbonate, water and dried with brine and over sodium sulphate and concentrated under reduced pressure. The residue was purified by flash column chromatography, eluting with ethyl acetate:petroleum ether (4:1 v/v) and neat ethyl acetate, to give the title compound as a colourless gum (1.22 g).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 20 h
  2. custompartitioned between ethyl acetate and 1M aqueous hydrochloric acid
  3. customThe aqueous layer was removed
  4. washthe organic phase washed with saturated aqueous sodium bicarbonate, water
  5. dry with materialdried with brine and over sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography
  8. washeluting with ethyl acetate:petroleum ether (4:1 v/v) and neat ethyl acetate

Sources & evidence

ORD record
ord-a533c4062a5a45f6aad1823deb33ca5a
Source dataset
uspto-grants-2001_12
Patent number
US06326386B1

Reaction notes

Loading…