Dichloromethane → (4-Methoxy-benzyl)-[4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]amine

HRID 1481541노트

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HRID 1481541 반응식
Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[CH:5]=[C:4]([C:18]([F:21])([F:20])[F:19])[CH:3]=1.[F:22][C:23]([F:34])([F:33])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+].C(Cl)Cl>COCCOC.O>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][NH:8][C:6]2[CH:5]=[C:4]([C:18]([F:21])([F:20])[F:19])[CH:3]=[C:2]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[C:23]([F:34])([F:33])[F:22])[N:7]=2)=[CH:11][CH:12]=1

참가 물질

7

반응물 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 86657407(6-Chloro-4-trifluoromethyl-pyridin-2-yl)-(4-methoxy-benzyl)-amine

생성물 1

HCID 86657408(4-Methoxy-benzyl)-[4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]amine

시약·촉매·용매 2

HCID 962Water용매2회HCID 80711,2-Dimethoxyethane용매

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온도
80 °C

실험 절차

A solution of (6-chloro-4-trifluoromethyl-pyridin-2-yl)-(4-methoxy-benzyl)-amine (7.26 g, 22.9 mmol, prepared as described in STEP A above) in DME (100 mL) and water (50 mL) was treated with 2-trifluoromethylphenylboronic acid (5.66 g, 29.8 mmol), and Cs2CO3 (11.2 g, 34.4 mmol). The resulting mixture was degassed via heating under a stream of Ar. Cl2Pd(dppf).DCM (1.13 g, 1.38 mmol) was added, and the mixture was heated to 80° C. for 4 h. The cooled mixture was diluted with water (100 mL) and extracted twice with EtOAc (150 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 115-g SEPRA Si 35 SPE column (Flow rate=30 mL/min; Eluent=EtOAc-hexanes, 1:99 for 10 min, then 1:99 to 1:4 over 40 min) to yield (4-methoxy-benzyl)-[4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amine as a yellow oil, which solidified upon standing. 1H-NMR (400 MHz, CDCl3) δ: 7.76 (d, J=7.8 Hz, 1H), 7.57-7.63 (m, 1H), 7.47-7.55 (m, 2H), 7.27 (d, J=8.6 Hz, 2H), 6.85-6.91 (m, 3H), 6.57 (s, 1H), 5.11 (t, J=5.2 Hz, 1H), 4.48 (d, J=5.6 Hz, 2H), 3.80 (s, 3H). Mass Spectrum (LCMS, APCI pos.): Calculated for C21H16N2OF6: 427.1 (M+H). Measured: 427.2.

후처리

  1. customThe resulting mixture was degassed
  2. temperaturevia heating under a stream of Ar
  3. extractionextracted twice with EtOAc (150 mL)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a 115-g SEPRA Si 35 SPE column (Flow rate=30 mL/min

출처 및 근거

ORD 기록
ord-ea0be64668574385bad618be87910d21
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409915B2

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