2-chloro-6,7-dimethoxy-N-(4-methylphenyl)quinazolin-4-amine → 4-[1-(6,7-Dimethoxy-4-p-tolylaminoquinazolin-2-yl)piperidin-4-ylamino]benzoic acid tert-butyl ester

HRID 1274123ノート

反応式

HRID 1274123 の反応式
Cl[C:2]1[N:11]=[C:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)[C:9]2[C:4](=[CH:5][C:6]([O:22][CH3:23])=[C:7]([O:20][CH3:21])[CH:8]=2)[N:3]=1.[C:24]([O:28][C:29](=[O:43])[C:30]1[CH:35]=[CH:34][C:33]([NH:36][CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)=[CH:32][CH:31]=1)([CH3:27])([CH3:26])[CH3:25]>C(O)CCCC>[C:24]([O:28][C:29](=[O:43])[C:30]1[CH:35]=[CH:34][C:33]([NH:36][CH:37]2[CH2:42][CH2:41][N:40]([C:2]3[N:11]=[C:10]([NH:12][C:13]4[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=4)[C:9]4[C:4](=[CH:5][C:6]([O:22][CH3:23])=[C:7]([O:20][CH3:21])[CH:8]=4)[N:3]=3)[CH2:39][CH2:38]2)=[CH:32][CH:31]=1)([CH3:27])([CH3:25])[CH3:26]

参加物

4

反応物 2

HCID 53288292-chloro-6,7-dimethoxy-N-(4-methylphenyl)quinazolin-4-amineHCID 106362074-(Piperidin-4-ylamino)benzoic Acid tert-Butyl Ester

生成物 1

HCID 99379424-[1-(6,7-Dimethoxy-4-p-tolylaminoquinazolin-2-yl)piperidin-4-ylamino]benzoic acid tert-butyl ester収率 85.4%

試薬・触媒・溶媒 1

HCID 62761-Pentanol溶媒

反応条件

温度
120 °C

実験手順

2-chloro-6,7-dimethoxy-N-(4-methylphenyl)-4-quinazolinamine (0.099 g, 0.3 mmol) prepared according to the procedures described in Gazit et al (Bioorg Med Chem, 1996, 4:1203) was added to a solution of (49) (0.10 g, 0.37 mmol) in n-pentanol (5 mL) at 25° C. The mixture was heated to 120° C. and maintained at that temperature for 12 h. The reaction mixture was then cooled to room temperature and the desired product was filtered and rinsed with acetone to give 0.146 g (85.3%) of the title compound: TLC (Rf =0.40; 5% MeOH/CH2Cl2); 1H NMR (DMSO) δ 12.41 (br s, 1H), 10.71 (br s, 1H), 8.08 (s, 1H), 7.63 (d, 2H, J=8.7), 7.57 (s, 1H), 7.55 (d, 2H, J=8.3), 7.24 (d, 2H, J=8.3), 6.63 (d, 2H, J=8.8), 6.44 (d, 1H, J=6.9), 4.41 (d, 2H, J=12.9), 3.91 (s, 3H), 3.89 (s, 3H), 3.73 (m, 1H), 3.42 (m, 2H), 2.31 (s, 3H), 2.03 (d, 2H, J=10.8), 1.49 (s, 9H), 1.41 (m, 2H); 13C NMR (DMSO) δ 165.2, 157.2, 155.2, 151.3, 150.7, 146.9, 136.6, 134.7, 130.9, 129.0, 124.0, 117.7, 111.2, 104.6, 102.3, 99.3, 79.0, 56.5, 56.1, 47.9, 43.7, 30.8, 28.0, 20.6; HRMS (FAB) m/z 570.3070 (M+H)+ (C33H39N5O4 requires 570.3080); Anal. (C33H39N5O4 ·1HCl) C, H, N.

後処理

  1. temperaturemaintained at that temperature for 12 h
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. filtrationthe desired product was filtered
  4. washrinsed with acetone

出典と根拠

ORDレコード
ord-e3ecffc9ba4045899b75228361dc5c8f
出典データセット
uspto-grants-2000_12
特許番号
US06156758

反応ノート

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