Water → HCID 117678157, 화합물

HRID 1778174노트

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HRID 1778174 반응식
[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]

참가 물질

6

반응물 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

생성물 1

HCID 117678157HCID 117678157, 화합물수율 53.7%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
90 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-0daa0c3e93554917aa07e05728cf66b9
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09266862B2

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