Hydrochloric Acid → N-(2-fluoro-4-methylphenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine

HRID 238105ノート

反応式

HRID 238105 の反応式
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:23][C:24]1[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][C:25]=1[NH2:26].Cl>C(O)(C)C>[F:23][C:24]1[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][C:25]=1[NH:26][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 679842-Fluoro-4-methylanilineHCID 117822304-Chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline

生成物 1

HCID 5329042N-(2-fluoro-4-methylphenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine収率 66.6%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒2 回

反応条件

温度
80 °C

実験手順

A suspension of 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (200 mg, 0.622 mmol), (prepared as described for the starting material in Example 2c) and 2-fluoro-4-methylaniline (94 mg, 0.764 mmol) in isopropanol (5 ml) containing 6.2M hydrogen chloride in isopropanol (110 μl) was stirred at 80° C. for 1.5 hours. After cooling, the precipitate was collected by filtration, washed with isopropanol, followed by ether and dried under vacuum. The solid was purified by column chromatography, eluting with methylene chloride/methanol (90/10) followed by 5% ammonia in methanol/methylene chloride (10/90). Evaporation of the fractions containing the expected product gave 4-(2-fluoro-4-methylanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (170 mg, 61%).

後処理

  1. custom(prepared
  2. temperatureAfter cooling
  3. filtrationthe precipitate was collected by filtration
  4. washwashed with isopropanol
  5. customdried under vacuum
  6. customThe solid was purified by column chromatography
  7. washeluting with methylene chloride/methanol (90/10)
  8. customEvaporation of the fractions
  9. additioncontaining the expected product

出典と根拠

ORDレコード
ord-ca90a0a384d24af3885d7a084dda448c
出典データセット
uspto-grants-2014_02
特許番号
US08642608B2

反応ノート

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