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

HRID 56377

反応式

HRID 56377 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
125 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-bc6fea8b125d4e8ebe4d6b090353c70d
出典データセット
uspto-grants-2016_09
特許番号
US09434700B2

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