Cesium carbonate → {1-[4-(Isoquinolin-6-ylamino)-1-(4-methoxy-phenyl)-cyclohexyl]-propyl}-carbamic acid benzyl ester

HRID 45197

反応式

HRID 45197 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.[CH2:12]([O:19][C:20](=[O:40])[NH:21][CH:22]([C:25]1([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[CH2:30][CH2:29][CH:28]([NH2:31])[CH2:27][CH2:26]1)[CH2:23][CH3:24])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:12]([O:19][C:20](=[O:40])[NH:21][CH:22]([C:25]1([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[CH2:26][CH2:27][CH:28]([NH:31][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH:8]=[N:7][CH:6]=[CH:5]3)[CH2:29][CH2:30]1)[CH2:23][CH3:24])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 3136816-BromoisoquinolineHCID 634876Binap, (A+-)-HCID 58380970{1-[4-Amino-1-(4-methoxy-phenyl)-cyclohexyl]-propyl}carbamic acid benzyl ester

生成物 1

HCID 67075630{1-[4-(Isoquinolin-6-ylamino)-1-(4-methoxy-phenyl)-cyclohexyl]-propyl}-carbamic acid benzyl ester収率 28.6%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

In 1 mL of absolute toluene were dissolved 66.0 mg (0.32 mmol) of 6-bromo-isoquinoline, 151 mg (380 μmol) of {1-[4-amino-1-(4-methoxy-phenyl)-cyclohexyl]-propyl}-carbamic acid benzyl ester (98), and 155 mg (476 μmol) of cesium carbonate. The solution was degassed twice, then 2.14 mg (9.5 μmol) of palladium acetate and 8.89 mg (14.3 μmol) of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl were added and the reaction mixture was heated to 100° C. until complete conversion could be observed. The mixture was evaporated, then redissolved in 50 mL of dichloromethane and washed twice with 50 mL of saturated aqueous sodium bicarbonate solution. The organic phase was dried over magnesium sulphate, filtered, concentrated and purified by silica gel chromatography (dichloromethane:methanol) to give 48 mg of the pure desired product. Rt=1.38 min (Method 19). Detected mass: 524.4 (M+H+).

後処理

  1. customThe solution was degassed twice
  2. customThe mixture was evaporated
  3. dissolutionredissolved in 50 mL of dichloromethane
  4. washwashed twice with 50 mL of saturated aqueous sodium bicarbonate solution
  5. dry with materialThe organic phase was dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography (dichloromethane:methanol)

出典と根拠

ORDレコード
ord-c82a7faf1ea04e85bdff193acf86afb6
出典データセット
uspto-grants-2013_09
特許番号
US08541449B2

関連ノート

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