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 2245070노트

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HRID 2245070 반응식
[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]

참가 물질

4

반응물 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

생성물 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 salt수율 70.8%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
50 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-386dbbe099b84a5f87241e660fed9ed8
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07678801B2

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