Hydrochloric Acid → Baricitinib

HRID 1692978ノート

反応式

HRID 1692978 の反応式
C(OC[N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([C:18]3[CH:19]=[N:20][N:21]([C:23]4([CH2:32][C:33]#[N:34])[CH2:26][N:25]([S:27]([CH2:30][CH3:31])(=[O:29])=[O:28])[CH2:24]4)[CH:22]=3)[C:12]=2[CH:11]=[CH:10]1)(=O)C(C)(C)C.O.[OH-].[Li+].Cl>C(#N)C.C(O)(C)C>[N:14]1[C:13]2[NH:9][CH:10]=[CH:11][C:12]=2[C:17]([C:18]2[CH:19]=[N:20][N:21]([C:23]3([CH2:32][C:33]#[N:34])[CH2:24][N:25]([S:27]([CH2:30][CH3:31])(=[O:28])=[O:29])[CH2:26]3)[CH:22]=2)=[N:16][CH:15]=1

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 66824167(4-(1-(3-(Cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)methyl pivalate

生成物 1

HCID 44205240Baricitinib収率 78.4%

試薬・触媒・溶媒 2

HCID 3776Isopropanol溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
47.5 °C

実験手順

Alternatively, a suspension of (4-(1-(3-(cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (20, 10.0 g, 20.6 mmol) and lithium hydroxide monohydrate (2.59 g, 61.8 mmol) in acetonitrile (CH3CN 40 mL) and isopropyl alcohol (10 mL) was heated at 45-50° C. for 6 hours. When HPLC showed that the reaction was deemed complete, the reaction mixture was cooled to room temperature and 1M hydrochloric acid aqueous solution (41 mL) as added to adjust the pH to 6-7 at temperature below 25° C. After the acid addition, the mixture was stirred at room temperature for 1 h and the precipitates were isolated by filtration. The wet cake was washed with water (50 mL) and dried in vacuum oven at 50° C. to give crude 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(ethylsulfonyl)azetidin-3-yl)acetonitrile (14, 6.0 g, 7.65 g theoretical, 78% yield) as off-white solids, which was found to be identical to the material prepared by Method A.

後処理

  1. temperaturethe reaction mixture was cooled to room temperature
  2. customat temperature below 25° C
  3. additionAfter the acid addition
  4. customthe precipitates were isolated by filtration
  5. washThe wet cake was washed with water (50 mL)
  6. customdried in vacuum oven at 50° C.

出典と根拠

ORDレコード
ord-0496026cee3b477cba0e2bc7c3a73dce
出典データセット
uspto-grants-2012_04
特許番号
US08158616B2

反応ノート

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