Methanesulfonic 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 methanesulfonate salt

HRID 2245070Notes

Reaction equation

HRID 2245070 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([NH:34][CH2:35][C:36]3[NH:37][CH:38]=[CH:39][N:40]=3)[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:30]=[CH:31][C:32]=3[CH3:33])[C:22]([NH:24][C:25]3[S:26][CH:27]=[CH:28][N:29]=3)=[O:23])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:41].[CH3:42][S:43]([OH:46])(=[O:45])=[O:44]>C(#N)C>[CH3:42][S:43]([OH:46])(=[O:45])=[O:44].[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([NH:34][CH2:35][C:36]3[NH:40][CH:39]=[CH:38][N:37]=3)[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:30]=[CH:31][C:32]=3[CH3:33])[C:22]([NH:24][C:25]3[S:26][CH:27]=[CH:28][N:29]=3)=[O:23])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:41]

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 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 574528453-{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 methanesulfonate saltYield 70.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

Using material as made above in Example 79c, a reaction vessel is charged with the 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 (11.0 mg) and acetonitrile (250 μL) at room temperature (RT). The mixture is warmed to about 50° C. To the warmed mixture is added 1 eq of methanesulfonic acid solution (1N in water). The temperature is maintained for a few minutes until the solution clarifies. Heating is discontinued and the mixture is allowed to cool to room temperature while shaking. Shaking is continued at room temperature overnight. The product is filtered and washed with THF. Place cake in crystallization dish and dry for several hrs in vacuo (house vacuum, 50° C., N2 bleed). The yield is 70.8% (9.1 mg) 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 methanesulfonate salt with a melting onset at 320° C. (determined by DSC).

Workup

  1. temperatureThe temperature is maintained for a few minutes until the solution
  2. temperatureHeating
  3. temperatureto cool to room temperature
  4. stirringShaking
  5. filtrationThe product is filtered
  6. washwashed with THF
  7. customin crystallization dish
  8. dry with materialdry for several hrs in vacuo (house vacuum, 50° C., N2 bleed)

Sources & evidence

ORD record
ord-386dbbe099b84a5f87241e660fed9ed8
Source dataset
uspto-grants-2010_03
Patent number
US07678801B2

Reaction notes

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