1-Hydroxybenzotriazole → 2-{(S)-2-[2-benzyloxycarbonylamino-2-(4-methoxy-3-methyl-phenyl)-acetylamino]-3-phenyl-propionylamino}-thiazole-4-carboxylic acid methyl ester

HRID 2222983

Reaction equation

HRID 2222983 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:21])[C@@H:12]([NH2:20])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[S:8][CH:9]=1)=[O:4].[CH2:22]([O:29][C:30]([NH:32][CH:33]([C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[C:39]([CH3:45])[CH:38]=1)[C:34](O)=[O:35])=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(C(C)C)CC)(C)C.ON1C2C=CC=CC=2N=N1.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:21])[C@@H:12]([NH:20][C:34](=[O:35])[CH:33]([NH:32][C:30]([O:29][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:31])[C:37]2[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[C:39]([CH3:45])[CH:38]=2)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[S:8][CH:9]=1)=[O:4]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 130500O-benzotriazol-1-yl-tetramethyluroniumHCID 68798586Benzyloxycarbonylamino-(4-methoxy-3-methyl-phenyl)-acetic acidHCID 866040402-((S)-2-amino-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester

Product 1

HCID 866040582-{(S)-2-[2-benzyloxycarbonylamino-2-(4-methoxy-3-methyl-phenyl)-acetylamino]-3-phenyl-propionylamino}-thiazole-4-carboxylic acid methyl esterYield 69.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-((S)-2-amino-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester (0.93 g, 3.04 mmol), benzyloxycarbonylamino-(4-methoxy-3-methyl-phenyl)-acetic acid (1.0 g, 3.04 mmol), diisopropylethylamine (2.1 mL, 12 mmol) and 1-hydroxybenzotriazole (0.46 g, 3.04 mmol) in N,N-dimethylformamide (10 mL) at 0° C. was added O-benzotriazol-1-yl-N,N, N′,N′-tetramethyluronium hexaflurorophosphate (1.15 g, 3.04 mmol). The reaction mixture was stirred at 0° C. for 2 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was separated, washed with water, brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography over silica gel eluted with 2:1 ethyl acetate/hexanes to give 2-{(S)-2-[2-benzyloxycarbonylamino-2-(4-methoxy-3-methyl-phenyl)-acetylamino]-3-phenyl-propionylamino}-thiazole-4-carboxylic acid methyl ester as a white solid (1.3 g, 69%).

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with water, brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography over silica gel
  7. washeluted with 2:1 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-4b1de5cdc0af479d9c55e082234a0818
Source dataset
uspto-grants-2008_05
Patent number
US07371869B2

Linked notes

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