4-Methoxybenzylamine → N4-(3,4-dichlorophenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine

HRID 511799ノート

反応式

HRID 511799 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[CH:19]=[C:18](F)[N:17]=[CH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:21][O:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][NH2:28])=[CH:25][CH:24]=1>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[CH:19]=[C:18]([NH:28][CH2:27][C:26]4[CH:29]=[CH:30][C:23]([O:22][CH3:21])=[CH:24][CH:25]=4)[N:17]=[CH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]

参加物

4

反応物 2

HCID 754524-MethoxybenzylamineHCID 68158723N-(3,4-dichlorophenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine

生成物 1

HCID 86668934N4-(3,4-dichlorophenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine収率 64%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
52 °C

実験手順

A mixture of compound 204 (2.95 g, 9.55 mmol) and 4-methoxybenzylamine (12.6 mL, 95.5 mmol) in dry DMSO (20 mL) was stirred under a nitrogen atmosphere at 52° C. (bath temperature) for 10 days. The solution was then cooled and petroleum ether (200 mL) was added. It was stirred at room temperature for 10 min. The layers were allowed to separate and the petroleum ether layer was decanted. This procedure was repeated with more petroleum ether (2×200 ml). Water (200 mL) was added and the mixture was stirred at room temperature for 15 min. It was filtered and washed solid with water (5×30 mL), then with petroleum ether (3×30 mL). The sticky yellow/orange solid was stirred with acetone (100 mL) at 35-45° C. (internal temperature) for 10 min. Water (100 mL) was added and stirred at room temperature for 20 min. The solid was collected by suction-filtration, washed with water/acetone (1:1) (5×20 mL), and dried in vacuum over silica-gel/KOH to give pure N4-(3,4-dichlorophenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine (213) (2.59 g, 64%) as a yellow/orange solid, mp 209-211° C.; 1H NMR δ [(CD3)2SO] 9.76 (s, 1H), 8.77 (s, 1H), 8.42 (s, 1H), 8.30 (poorly resolved d, J=2.1 Hz, 1H), 7.89 (dd, J=8.8, 2.1 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.38-7.25 (m, 3H), 7.17 (s, 1H), 6.92-6.83 (m, 2H), 4.49 (d, J=6.3 Hz, 2H), 3.71 (s, 3H). Anal. Calcd for C21H17Cl2N5O: C, 59.17; H, 4.02; N, 16.43%. Found C, 58.93; H, 4.17; N, 16.12%.

後処理

  1. temperatureThe solution was then cooled
  2. stirringIt was stirred at room temperature for 10 min
  3. customto separate
  4. customthe petroleum ether layer was decanted
  5. additionWater (200 mL) was added
  6. stirringthe mixture was stirred at room temperature for 15 min
  7. filtrationIt was filtered
  8. washwashed solid with water (5×30 mL)
  9. stirringThe sticky yellow/orange solid was stirred with acetone (100 mL) at 35-45° C. (internal temperature) for 10 min
  10. additionWater (100 mL) was added
  11. stirringstirred at room temperature for 20 min
  12. filtrationThe solid was collected by suction-filtration
  13. washwashed with water/acetone (1:1) (5×20 mL)
  14. dry with materialdried in vacuum over silica-gel/KOH

出典と根拠

ORDレコード
ord-7ae539e6985c439bb58837481f559973
出典データセット
uspto-grants-2015_08
特許番号
US09101632B2

反応ノート

読み込み中…