Water → HCID 117678157、化合物

HRID 1778174ノート

反応式

HRID 1778174 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12](Cl)[N:11]=[C:10]([N:15]3[CH2:20][C@@H:19]4[CH2:21][C@H:16]3[CH2:17][N:18]4[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH:9]=2)=[CH:4][C:3]=1[C:29]([F:32])([F:31])[F:30].Cl.[CH:34]12[CH2:39][CH:37]([CH2:38]1)[CH2:36][NH:35]2.C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([N:35]3[CH2:36][CH:37]4[CH2:39][CH:34]3[CH2:38]4)[N:11]=[C:10]([N:15]3[CH2:20][C@@H:19]4[CH2:21][C@H:16]3[CH2:17][N:18]4[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH:9]=2)=[CH:4][C:3]=1[C:29]([F:32])([F:31])[F:30]

参加物

6

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 552197462-Azabicyclo(2.1.1)hexane hydrochlorideHCID 117678278(1S,4S)-tert-butyl 5-(6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-2-chloropyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

生成物 1

HCID 117678157HCID 117678157、化合物収率 53.7%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
90 °C

実験手順

To a solution of (1S,4S)-tert-butyl 5-(6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-2-chloropyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (220 mg, 0.47 mmol) in DMSO (2 mL) was added 2-azabicyclo[2.1.1]hexane hydrochloride (68 mg, 0.56 mmol) and potassium carbonate (130 mg, 0.93 mmol). The mixture was heated at 90° C. for 16 h. After cooling to room temperature, water (50 mL) was added to. The mixture was extracted with ethyl acetate (30 mL (3 times)). The organic layer was dried over sodium sulfate, concentrated and purified by flash column chromatography (50% ethyl acetate in petroleum ether to 100% ethyl acetate) to provide (1S,4S)-tert-butyl 5-(6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-2-(2-azabicyclo[2.1.1]hexan-2-yl)pyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (130 mg, 53.7% yield). LCMS (ESI): [MH]+=518.0.

後処理

  1. temperatureAfter cooling to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (30 mL (3 times))
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (50% ethyl acetate in petroleum ether to 100% ethyl acetate)

出典と根拠

ORDレコード
ord-0daa0c3e93554917aa07e05728cf66b9
出典データセット
uspto-grants-2016_02
特許番号
US09266862B2

反応ノート

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