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 1186119ノート

反応式

HRID 1186119 の反応式
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

参加物

4

反応物 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

生成物 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)-amine収率 86%

試薬・触媒・溶媒 1

HCID 2631-Butanol溶媒

反応条件

温度
160 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-a09e000d6d214541898b6bfc24324b1c
出典データセット
uspto-grants-2014_03
特許番号
US08673895B2

反応ノート

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