1-Methylimidazole → (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-N-(5-fluoro-2-pyridinyl)-1-methyl-3-pyrazolidinecarboxamide

HRID 1396888Notes

Reaction equation

CN1C=CN=C1.[CH:7]1([CH2:12][C@H:13]([CH2:34][N:35]([CH:44]=[O:45])[O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:14]([N:16]2[C@H:20]([C:21](O)=[O:22])[CH2:19][CH2:18][N:17]2[C:24](OCC2C=CC=CC=2)=O)=[O:15])[CH2:11][CH2:10][CH2:9][CH2:8]1.S(Cl)(C)(=O)=O.[F:51][C:52]1[CH:53]=[CH:54][C:55]([NH2:58])=[N:56][CH:57]=1>CN(C=O)C>[CH:7]1([CH2:12][C@H:13]([CH2:34][N:35]([CH:44]=[O:45])[O:36][CH2:37][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:14]([N:16]2[C@H:20]([C:21]([NH:58][C:55]3[CH:54]=[CH:53][C:52]([F:51])=[CH:57][N:56]=3)=[O:22])[CH2:19][CH2:18][N:17]2[CH3:24])=[O:15])[CH2:8][CH2:9][CH2:10][CH2:11]1

Participants

Conditions

Temperature: 0 °C

Procedure

1-Methylimidazole (38.2 μl, 0.479 mmol) was added into a solution of (3S)-2-[(2R)-3-cyclopentyl-2({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidine carboxylic acid (100 mg, 0.240 mmol) in 1.0 ml of DMF. The solution was cooled to 0° C., and then mesyl chloride (24.26 μl, 0.311 mmol) was added dropwise at 0° C. and then 5-fluoro-2-pyridinamine (40.3 mg, 0.359 mmol) dissolved in another 1.0 ml of DMF was added. The reaction mixture was stirred for 3.5 h at rt. The reaction mixture was concentrated and purified by RP-HPLC to afford (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-N-(5-fluoro-2-pyridinyl)-1-methyl-3-pyrazolidinecarboxamide (84 mg, 0.164 mmol, 68.6% yield) as a white solid. LC-MS (ES) m/e 512.3 (M+H)+.

Workup

additionwas added
concentrationThe reaction mixture was concentrated
custompurified by RP-HPLC

Sources & evidence

ORD record: ord-9ef51038da354c999e3330ed085d3fa2
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901119B2

Reaction notes

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