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

HRID 76055노트

반응식

HRID 76055 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 22595558Toluene tert-butyl alcohol용매

반응 조건

온도
150 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b4ecf67b3f4840b590ccb9c4c45b5410
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835451B2

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