Sulfuric Acid → 3-{8-(2,6-difluorophenyl)-2-[(1H-imidazol-2-ylmethyl)amino]-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl}-4-methyl-N-1,3-thiazol-2-ylbenzamide sulfate

HRID 222983Notes

Reaction equation

C(#N)C.[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:6]=1[N:12]1[C:17]2[N:18]=[C:19]([NH:37][CH2:38][C:39]3[NH:40][CH:41]=[CH:42][N:43]=3)[N:20]=[C:21]([C:22]3[CH:23]=[C:24]([CH:33]=[CH:34][C:35]=3[CH3:36])[C:25]([NH:27][C:28]3[S:29][CH:30]=[CH:31][N:32]=3)=[O:26])[C:16]=2[CH:15]=[CH:14][C:13]1=[O:44].[S:45](=[O:49])(=[O:48])([OH:47])[OH:46]>O>[S:45]([OH:49])([OH:48])(=[O:47])=[O:46].[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:6]=1[N:12]1[C:17]2[N:18]=[C:19]([NH:37][CH2:38][C:39]3[NH:43][CH:42]=[CH:41][N:40]=3)[N:20]=[C:21]([C:22]3[CH:23]=[C:24]([CH:33]=[CH:34][C:35]=3[CH3:36])[C:25]([NH:27][C:28]3[S:29][CH:30]=[CH:31][N:32]=3)=[O:26])[C:16]=2[CH:15]=[CH:14][C:13]1=[O:44]

Participants

Conditions

Temperature: 50 °C

Procedure

Acetonitrile (250 uL) was added to amorphous free-base version of 3-{8-(2,6-difluorophenyl)-2-[(1H-imidazol-2-ylmethyl)amino]-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl}-4-methyl-N-1,3-thiazol-2-ylbenzamide from Example 79c (11.2 mg), and the resulting mixture was heated to about 50° C. Sulfuric acid was added (1.0 equivalent; 1N in water). The mixture was cooled to room temperature and shook for several hours. The product was filtered, washed with acetonitrile, and dried for several hours in a vacuum oven at about 50° C. with a slow nitrogen bleed. The yield was 72.5% (9.5 mg) of title compound (melt begins around 50° C. by DSC).

Workup

temperatureThe mixture was cooled to room temperature
filtrationThe product was filtered
washwashed with acetonitrile
customdried for several hours in a vacuum oven at about 50° C. with a slow nitrogen

Sources & evidence

ORD record: ord-908d0093d95140fdbf8a58b88cc6fa2a
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207176B2

Reaction notes

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