Citric 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 citrate

HRID 222985Notes

Reaction equation

HRID 222985 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:58])(=[O:57])[CH2:47][C:48]([CH2:53][C:54]([OH:56])=[O:55])([C:50]([OH:52])=[O:51])[OH:49]>C1COCC1>[C:46]([OH:58])(=[O:57])[CH2:47][C:48]([CH2:53][C:54]([OH:56])=[O:55])([C:50]([OH:52])=[O:51])[OH:49].[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

5

Reactant 3

HCID 311Citric AcidHCID 3776IsopropanolHCID 119481803-{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

Product 1

HCID 866085703-{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 citrateYield 61.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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 (10.6 mg), and the resulting mixture was heated to 50° C. Citric acid was added (1.0 equivalent; 1N in THF). The mixture was cooled to room temperature and shook for several days. The product was filtered, washed with isopropanol, and dried for several hours in a vacuum oven at 50° C. with a slow nitrogen bleed. The yield was 61.4% (8.7 mg) of title compound with a melting onset at 179° C. (determined by DSC).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationThe product was filtered
  3. washwashed with isopropanol
  4. customdried for several hours in a vacuum oven at 50° C. with a slow nitrogen

Sources & evidence

ORD record
ord-81392fcac1a4482984885cc5c8b08dcf
Source dataset
uspto-grants-2012_06
Patent number
US08207176B2

Reaction notes

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