1-Methylimidazole → (5S)-1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-N-4-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamide

HRID 1396934Notes

Reaction equation

CN1C=CN=C1.[CH:7]1([CH2:12][C@H:13]([CH2:24][N:25]([CH:34]=[O:35])[O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:14]([N:16]2[C@H:20]([C:21]([OH:23])=O)[CH2:19][CH:18]=[N:17]2)=[O:15])[CH2:11][CH2:10][CH2:9][CH2:8]1.S(Cl)(C)(=O)=O.[N:41]1[CH:46]=[CH:45][C:44]([NH2:47])=[N:43][CH:42]=1>CN(C)C=O>[CH:7]1([CH2:12][C@H:13]([CH2:24][N:25]([CH:34]=[O:35])[O:26][CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:14]([N:16]2[C@H:20]([C:21]([NH:47][C:44]3[CH:45]=[CH:46][N:41]=[CH:42][N:43]=3)=[O:23])[CH2:19][CH:18]=[N:17]2)=[O:15])[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

Conditions

Temperature: 0 °C

Procedure

1-Methylimidazole (39.7 μl, 0.498 mmol) was added into the solution of (55)-1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-4,5-dihydro-1H-pyrazole-5-carboxylic acid (100 mg, 0.249 mmol) in N,N-dimethylformamide (DMF) (1.8 ml). The resulting solution was cooled to 0° C., and then mesyl chloride (20.24 μl, 0.262 mmol) was added dropwise at 0° C. To the reaction mixture was added 4-pyrimidinamine (26.1 mg, 0.274 mmol). After stirring for 2 h 10 min at ambient temperature, the reaction solution was purified by RP-HPLC to yield (5S)-1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-N-4-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamide (76 mg, 0.159 mmol, 64% yield). MS (ES+) m/z 478.8 (MH+).

Workup

customthe reaction solution was purified by RP-HPLC

Sources & evidence

ORD record: ord-087bcefac811473a81f1fa036ae97017
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901119B2

Reaction notes

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