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 1806565ノート

反応式

HRID 1806565 の反応式
[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]

参加物

4

反応物 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

生成物 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 salt収率 70.8%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
50 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-8cef6b0283cb49849b059a9b23301c15
出典データセット
uspto-grants-2013_01
特許番号
US08354416B2

反応ノート

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