Cesium carbonate → tert-butyl ((1S,2R)-2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)cyclohexyl)carbamate

HRID 56377

반응식

HRID 56377 반응식
Cl[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]3[C:17]([Cl:18])=[C:16]([O:19][CH3:20])[CH:15]=[C:14]([O:21][CH3:22])[C:13]=3[Cl:23])[CH:8]=2)[N:3]=1.[NH2:24][C@H:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]1[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35].C([O-])([O-])=O.[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>CC(N(C)C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:23][C:13]1[C:14]([O:21][CH3:22])=[CH:15][C:16]([O:19][CH3:20])=[C:17]([Cl:18])[C:12]=1[C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([NH:24][C@@H:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]1[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])[N:11]=[CH:10]2

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 1514391tert-butyl N-[(1S,2S)-2-aminocyclohexyl]carbamateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 899217722-Chloro-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazoline

생성물 1

HCID 118043439tert-butyl ((1S,2R)-2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)cyclohexyl)carbamate수율 45.3%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 31374Dimethylacetamide용매

반응 조건

온도
125 °C

실험 절차

A mixture of 2-chloro-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazoline (0.1 g, 0.27 mmol), tert-butyl ((1S,2S)-2-aminocyclohexyl)carbamate (75 mg, 0.35 mmol), Cs2CO3 (176 mg, 0.54 mmol), X-Phos (13 mg, 0.027 mmol) and Pd2dba3 (12.5 mg, 0.013 mmol) in DMA (1.8 mL) was degassed with N2 for 5 mins and heated in a microwave reactor at 125° C. for 30 mins. The mixture was cooled to room temperature, filtered through celite and washed with water followed by saturated brine solution. The residue was purified by silica gel column chromatography to afford tert-butyl ((1S,2R)-2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)cyclohexyl)carbamate (67 mg, 45%). MS (ES+) C27H32Cl2N4O4 requires: 546, found: 547 [M+H]+.

후처리

  1. customwas degassed with N2 for 5 mins
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered through celite
  4. washwashed with water
  5. customThe residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-bc6fea8b125d4e8ebe4d6b090353c70d
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434700B2

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