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

HRID 238105노트

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HRID 238105 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 3776Isopropanol용매2회

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온도
80 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-ca90a0a384d24af3885d7a084dda448c
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642608B2

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