4-(Trifluoromethyl)aniline → [2-Methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine

HRID 1485349노트

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HRID 1485349 반응식
Cl[C:2]1[C:12]2[CH2:11][CH2:10][N:9]([C:13]3[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:16]=[CH:15][N:14]=3)[CH2:8][CH2:7][C:6]=2[N:5]=[C:4]([S:23][CH3:24])[N:3]=1.[F:25][C:26]([F:35])([F:34])[C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1>CCCCO>[CH3:24][S:23][C:4]1[N:3]=[C:2]([NH:31][C:30]2[CH:32]=[CH:33][C:27]([C:26]([F:25])([F:34])[F:35])=[CH:28][CH:29]=2)[C:12]2[CH2:11][CH2:10][N:9]([C:13]3[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:16]=[CH:15][N:14]=3)[CH2:8][CH2:7][C:6]=2[N:5]=1

참가 물질

4

반응물 2

HCID 99644-(Trifluoromethyl)anilineHCID 866153084-Chloro-2-methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine

생성물 1

HCID 58972614[2-Methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine수율 86%

시약·촉매·용매 1

HCID 2631-Butanol용매

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온도
160 °C

실험 절차

To a solution of 4-chloro-2-methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine (830 mg, 2.22 mmol) in n-BuOH (5 mL) was added 4-trifluoromethylaniline (0.4 mL, 3.30 mmol). The mixture was heated in the microwave at 160° C. for 30 min, then was cooled to rt, quenched with satd. aq. NaHCO3, and extracted with EtOAc. The combined organic layers were dried (MgSO4) and concentrated. The residue was purified (FCC) to give the title compound (950 mg, 86%). MS (ESI): mass calcd. for C22H19F6N5S, 499.13; m/z found, 500.1 [M+H]+. 1H NMR (CDCl3): 8.40-8.37 (m, 1H), 7.89-7.86 (m, 1H), 7.69 (d, J=8.6 Hz, 2H), 7.58 (d, J=9.1 Hz, 2H), 6.99-6.94 (m, 1H), 6.65 (s, 1H), 3.66-3.62 (m, 2H), 3.60-3.56 (m, 2H), 3.21-3.16 (m, 2H), 2.99-2.94 (m, 2H), 2.53 (s, 3H).

후처리

  1. temperaturewas cooled to rt
  2. customquenched with satd
  3. extractionaq. NaHCO3, and extracted with EtOAc
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified (FCC)

출처 및 근거

ORD 기록
ord-ed375d80c5c74d69855fa12bbcce11c0
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422293B2

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