p-Toluenesulfonic 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 4-methylbenzenesulfonate

HRID 222982Notes

Reaction equation

HRID 222982 reaction equation
C1COCC1.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:8]=1[N:14]1[C:19]2[N:20]=[C:21]([NH:39][CH2:40][C:41]3[NH:42][CH:43]=[CH:44][N:45]=3)[N:22]=[C:23]([C:24]3[CH:25]=[C:26]([CH:35]=[CH:36][C:37]=3[CH3:38])[C:27]([NH:29][C:30]3[S:31][CH:32]=[CH:33][N:34]=3)=[O:28])[C:18]=2[CH:17]=[CH:16][C:15]1=[O:46].[CH3:47][C:48]1[CH:53]=[CH:52][C:51]([S:54]([OH:57])(=[O:56])=[O:55])=[CH:50][CH:49]=1>O>[CH3:47][C:48]1[CH:49]=[CH:50][C:51]([S:54]([OH:57])(=[O:56])=[O:55])=[CH:52][CH:53]=1.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:8]=1[N:14]1[C:19]2[N:20]=[C:21]([NH:39][CH2:40][C:41]3[NH:45][CH:44]=[CH:43][N:42]=3)[N:22]=[C:23]([C:24]3[CH:25]=[C:26]([CH:35]=[CH:36][C:37]=3[CH3:38])[C:27]([NH:29][C:30]3[S:31][CH:32]=[CH:33][N:34]=3)=[O:28])[C:18]=2[CH:17]=[CH:16][C:15]1=[O:46]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 8028TetrahydrofuranHCID 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 874273103-{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 4-methylbenzenesulfonateYield 32.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

THF (17.5 mL) 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 (762.2 mg) at room temperature resulting in a clear solution. P-toluenesulfonic acid was added (0.4 equivalent; 1N in water), and the mixture stirred for several hours. The product was filtered, washed with THF, and dried overnight in a vacuum oven at 50° C. with a slow nitrogen bleed. The yield was 32.9% (327.0 mg) of the title compound with a melting onset at 259° C. (determined by DSC).

Workup

  1. customresulting in a clear solution
  2. filtrationThe product was filtered
  3. washwashed with THF
  4. customdried overnight in a vacuum oven at 50° C. with a slow nitrogen

Sources & evidence

ORD record
ord-d49f95f133ea473baaf9cd13ca5d5b4e
Source dataset
uspto-grants-2012_06
Patent number
US08207176B2

Reaction notes

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