Isopropanol → 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 fumarate

HRID 1806573Notes

Reaction equation

C(O)(C)C.[F:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:7]=1[N:13]1[C:18]2[N:19]=[C:20]([NH:38][CH2:39][C:40]3[NH:41][CH:42]=[CH:43][N:44]=3)[N:21]=[C:22]([C:23]3[CH:24]=[C:25]([CH:34]=[CH:35][C:36]=3[CH3:37])[C:26]([NH:28][C:29]3[S:30][CH:31]=[CH:32][N:33]=3)=[O:27])[C:17]=2[CH:16]=[CH:15][C:14]1=[O:45].[C:46]([OH:53])(=[O:52])/[CH:47]=[CH:48]/[C:49]([OH:51])=[O:50]>C(O)C>[C:46]([OH:53])(=[O:52])/[CH:47]=[CH:48]/[C:49]([OH:51])=[O:50].[F:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:7]=1[N:13]1[C:18]2[N:19]=[C:20]([NH:38][CH2:39][C:40]3[NH:44][CH:43]=[CH:42][N:41]=3)[N:21]=[C:22]([C:23]3[CH:24]=[C:25]([CH:34]=[CH:35][C:36]=3[CH3:37])[C:26]([NH:28][C:29]3[S:30][CH:31]=[CH:32][N:33]=3)=[O:27])[C:17]=2[CH:16]=[CH:15][C:14]1=[O:45]

Participants

Conditions

Temperature: 50 °C

Procedure

Isopropanol (200 uL) was added to 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 (10.5 mg), and the resulting mixture was heated to 50° C. Fumaric acid was added (1.0 equivalent; 0.2 N in ethanol). The mixture was cooled to room temperature and shook for several days. The product was filtered, washed with isopropanol, and dried overnight in a vacuum oven at 50° C. with a slow nitrogen bleed. The yield was 61.4% (6.0 mg) of title compound with a melting onset at 251° C. (determined by DSC).

Workup

temperatureThe mixture was cooled to room temperature
filtrationThe product was filtered
washwashed with isopropanol
customdried overnight in a vacuum oven at 50° C. with a slow nitrogen

Sources & evidence

ORD record: ord-bd196c9be3bd4ed4a299a183af7fe278
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354416B2

Reaction notes

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