Cesium carbonate → Methyl 2-((1r,4r)-4-(4-(5-((6-(trifluoromethyl)pyridin-3-yl)amino)pyridin-2-yl)phenyl)cyclohexyl)acetate

HRID 76055ノート

反応式

HRID 76055 の反応式
[CH3:1][O:2][C:3](=[O:24])[CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20](Br)=[CH:19][N:18]=3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.[NH2:25][C:26]1[CH:27]=[N:28][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1.C(O)(C)(C)C>[CH3:1][O:2][C:3](=[O:24])[CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([NH:25][C:26]4[CH:27]=[N:28][C:29]([C:32]([F:35])([F:33])[F:34])=[CH:30][CH:31]=4)=[CH:19][N:18]=3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 27377445-Amino-2-(trifluoromethyl)pyridineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 66615782Methyl 2-[4-[4-(5-bromopyridin-2-yl)phenyl]cyclohexyl]acetate

生成物 1

HCID 24938267Methyl 2-((1r,4r)-4-(4-(5-((6-(trifluoromethyl)pyridin-3-yl)amino)pyridin-2-yl)phenyl)cyclohexyl)acetate

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 22595558Toluene tert-butyl alcohol溶媒

反応条件

温度
150 °C

実験手順

A microwave vial was charged with {4-[4-(5-bromo-pyridin-2-yl)-phenyl]-cyclohexyl}-acetic acid methyl ester (3.4 g, 8.8 mmol, 1.0 equiv), 3-amino-6-trifluoromethyl pyridine (2.1 g, 13.1 mmol, 1.2 equiv), cesium carbonate (7.1 g, 21.9 mmol, 2.5 equiv), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-Phos, 0.42 g, 0.88 mmol, 0.1 equiv) and palladium acetate (0.30 g, 0.44 mmol, 0.05 equiv) in 20 Ml of toluene/t-butanol (9:1). The suspension was sparged with nitrogen for 10 min, then heated to 150° C. under microwave heating for 45 min. The reaction was cooled to room temperature, partitioned between ethyl acetate and water. The organic extracts were washed with brine, then dried over sodium sulphate and concentrated in vacuo. Purification by silica gel chromatography afforded the title compound: 1H NMR (400 MHz, DMSO-d6) δ 1.10-1.21 (m, 1H) 1.51 (qd, J=12.72, 2.78 Hz, 2H) 1.70-1.87 (m, 5H) 2.26 (d, J=6.57 Hz, 2H) 2.50 (m, 1H) 3.61 (s, 3H) 7.33 (d, J=8.34 Hz, 2H) 7.65 (d, J=2.53 Hz, 1H) 7.67-7.74 (m, 2H) 7.89 (d, J=8.59 Hz, 1H) 7.95 (d, J=8.34 Hz, 2H) 8.46 (d, J=2.53 Hz, 1H) 8.54 (d, J=2.53 Hz, 1H) 9.18 (s, 1H); (M+H)+427.3.

後処理

  1. customThe suspension was sparged with nitrogen for 10 min
  2. temperatureheating for 45 min
  3. temperatureThe reaction was cooled to room temperature
  4. custompartitioned between ethyl acetate and water
  5. washThe organic extracts were washed with brine
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated in vacuo
  8. customPurification by silica gel chromatography

出典と根拠

ORDレコード
ord-b4ecf67b3f4840b590ccb9c4c45b5410
出典データセット
uspto-grants-2014_09
特許番号
US08835451B2

反応ノート

読み込み中…