1-Methylimidazole → 2-propen-1-yl (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-3-[(2-pyrimidinylamino)carbonyl]-1-pyrazolidinecarboxylate

HRID 1396916Notes

Reaction equation

CN1C=CN=C1.[CH:7]1([CH2:12][C@H:13]([CH2:30][N:31]([CH:39]=[O:40])[O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[C:14]([N:16]2[CH:20]([C:21]([OH:23])=O)[CH2:19][CH2:18][N:17]2[C:24]([O:26][CH2:27][CH:28]=[CH2:29])=[O:25])=[O:15])[CH2:11][CH2:10][CH2:9][CH2:8]1.S(Cl)(C)(=O)=O.[N:46]1[CH:51]=[CH:50][CH:49]=[N:48][C:47]=1[NH2:52]>CN(C)C=O>[CH:7]1([CH2:12][C@H:13]([CH2:30][N:31]([CH:39]=[O:40])[O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[C:14]([N:16]2[C@H:20]([C:21]([NH:52][C:47]3[N:48]=[CH:49][CH:50]=[CH:51][N:46]=3)=[O:23])[CH2:19][CH2:18][N:17]2[C:24]([O:26][CH2:27][CH:28]=[CH2:29])=[O:25])=[O:15])[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

Conditions

Temperature: 0 °C

Procedure

1-Methylimidazole (38.1 μl, 0.478 mmol) was added into the solution of 2-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-1-[(2-propen-1-yloxy)carbonyl]-3-pyrazolidinecarboxylic acid (115 mg, 0.239 mmol) in N,N-dimethylformamide (DMF) (1.6 ml). The resulting solution was cooled to 0° C., and then mesyl chloride (19.41 μl, 0.251 mmol) was added dropwise at 0° C. To the reaction mixture was added 2-pyrimidinamine (34.1 mg, 0.358 mmol). After stirring for 3.5 hrs at ambient temperature, the reaction solution was purified by RP-HPLC to yield 2-propen-1-yl (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-3-[(2-pyrimidinylamino)carbonyl]-1-pyrazolidinecarboxylate (32 mg, 0.057 mmol, 24% yield). MS (ES+) m/z 559.0 (MH+).

Workup

customthe reaction solution was purified by RP-HPLC

Sources & evidence

ORD record: ord-edfb4fae7b574f0898346cb4be5ab767
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901119B2

Reaction notes

Loading…