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

HRID 511804ノート

反応式

HRID 511804 の反応式
[Br: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>[Br: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 68158622N-(3-bromo-4-chlorophenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine

生成物 1

HCID 86668937N4-(3-bromo-4-chlorophenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine収率 73.2%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
59 °C

実験手順

A mixture of compound 205 (3.09 g, 8.74 mmol) and 4-methoxybenzylamine (11.5 mL, 87.4 mmol) in dry DMSO (20 mL) was stirred under a nitrogen atmosphere at 58-60° C. (bath temperature) for a week. The solution was then cooled and petroleum ether (300 mL) was added. It was stirred at room temperature for 20 min. The layers were allowed to separate and the petroleum ether layer was decanted. This procedure was repeated once more with petroleum ether (300 mL). Water (250 mL) was added and the mixture was stirred at room temperature for 20 h. The yellow/orange solid was collected by filtration and washed with water (5×20 mL), then with petroleum ether (3×30 mL). The sticky yellow/orange solid was dissolved in acetone (150 mL) at 45° C. (bath temperature). It was filtered to remove insoluble impurities. To the filtrate was added water (400 mL) and stirred at room temperature for 1 h. The solid was collected by suction-filtration, washed with water (5×25 mL), petroleum ether (3×30 mL), and dried in vacuum over silica-gel/KOH to give pure N4-(3-bromo-4-chlorophenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine (214) (3.01 g, 73%) as a greenish yellow solid, mp 207-210° C.; 1H NMR δ [(CD)2SO] 9.74 (s, 1H), 8.77 (s, 1H), 8.41 (s, 1H), 8.39 (d, J=2.4 Hz, 1H), 7.96 (dd, J=8.8, 2.4 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.38-7.25 (m, 3H), 7.17 (s, 1H), 6.92-6.85 (m, 2H), 4.49 (d, J=6.3 Hz, 3.71 (s, 3H). Anal. Calcd for C21H17BrClN5O: C, 53.58; H, 3.64; N, 14.88%. Found C, 53.84; H, 3.55; N, 14.63%.

後処理

  1. temperatureThe solution was then cooled
  2. stirringIt was stirred at room temperature for 20 min
  3. customto separate
  4. customthe petroleum ether layer was decanted
  5. additionWater (250 mL) was added
  6. stirringthe mixture was stirred at room temperature for 20 h
  7. filtrationThe yellow/orange solid was collected by filtration
  8. washwashed with water (5×20 mL)
  9. dissolutionThe sticky yellow/orange solid was dissolved in acetone (150 mL) at 45° C. (bath temperature)
  10. filtrationIt was filtered
  11. customto remove insoluble impurities
  12. additionTo the filtrate was added water (400 mL)
  13. stirringstirred at room temperature for 1 h
  14. filtrationThe solid was collected by suction-filtration
  15. washwashed with water (5×25 mL), petroleum ether (3×30 mL)
  16. dry with materialdried in vacuum over silica-gel/KOH

出典と根拠

ORDレコード
ord-01d0f03522dd4ccaaa261daabd8cbd88
出典データセット
uspto-grants-2015_08
特許番号
US09101632B2

反応ノート

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