Ammonium Chloride → 2-{(S)-3-(4-amino-phenyl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-propionylamino}-thiazole-4-carboxylic acid methyl ester

HRID 2222971Notes

Reaction equation

HRID 2222971 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:38])[C@@H:12]([N:23]2[C:27](=[O:28])[C@@H:26]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)[NH:25][C:24]2=[O:37])[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[CH:16][CH:15]=2)[S:8][CH:9]=1)=[O:4].[Cl-].[NH4+]>CO.O1CCCC1.CN(C)C=O.O.[Zn]>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:38])[C@@H:12]([N:23]2[C:27](=[O:28])[C@@H:26]([C:29]3[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=3)[NH:25][C:24]2=[O:37])[CH2:13][C:14]2[CH:15]=[CH:16][C:17]([NH2:20])=[CH:18][CH:19]=2)[S:8][CH:9]=1)=[O:4]

Participants

8

Reactant 2

HCID 25517Ammonium ChlorideHCID 586154962-[(S)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-(4-nitro-phenyl)-propionylamino]-thiazole-4-carboxylic acid methyl ester

Product 1

HCID 586154572-{(S)-3-(4-amino-phenyl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-propionylamino}-thiazole-4-carboxylic acid methyl esterYield 22%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-[(S)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-(4-nitro-phenyl)-propionylamino]-thiazole-4-carboxylic acid methyl ester (0.32 g, 0.59 mmol) in methanol (125 mL), tetrahydrofuran (25 mL) and N,N-dimethylformamide (3 mL) was added a solution of ammonium chloride (0.63 g, 11.8 mmol) in water (3 mL) followed by zinc dust (<10 μM particle size) (0.388 g, 5.94 mmol). After 15 minutes the reaction mixture was filitered through a pad of Celite® and washed through with methanol. The filtrate was concentrated in vacuo and the residue partitioned between dichloromethane and water. The organic solution was washed with saturated aqueous sodium bicarbonate, water, brine, dried over sodium sulfate and concentrated in vacuo to a yellow solid (0.35 g). Purification by chromatography using silica eluted with 90:10:6:5 chloroform/water/acetic acid/methanol followed by drying in vacuo gave 2-{(S)-3-(4-amino-phenyl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-propionylamino}-thiazole-4-carboxylic acid methyl ester as a brown solid (66 mg, 22%).

Workup

  1. washwashed through with methanol
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue partitioned between dichloromethane and water
  4. washThe organic solution was washed with saturated aqueous sodium bicarbonate, water, brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo to a yellow solid (0.35 g)
  7. customPurification by chromatography
  8. washeluted with 90:10:6:5 chloroform/water/acetic acid/methanol
  9. customby drying in vacuo

Sources & evidence

ORD record
ord-5b70f31c9b504a21aa2800be90d34f40
Source dataset
uspto-grants-2008_05
Patent number
US07371869B2

Reaction notes

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