Acetyl chloride → 6-(1-Acetylpiperidin-4-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline

HRID 1948903노트

반응식

HRID 1948903 반응식
[C:1](Cl)(=[O:3])[CH3:2].Cl.Cl.[NH:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][C:23]=2[O:24][CH3:25])[N:20]=[CH:19][N:18]=[C:17]3[NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[C:28]=2[F:34])[CH2:9][CH2:8]1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][C:23]=2[O:24][CH3:25])[N:20]=[CH:19][N:18]=[C:17]3[NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[C:28]=2[F:34])[CH2:9][CH2:8]1)(=[O:3])[CH3:2]

참가 물질

5

반응물 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 574768654-(3-Chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-4-yloxy)quinazoline dihydrochloride

생성물 1

HCID 104336176-(1-Acetylpiperidin-4-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline수율 70%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

Acetyl chloride (179 mg) was added to a solution of 6-(piperidin-4-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline dihydrochloride (1 g) and diisopropylethylamine (735 mg) in methylene chloride that was cooled at 0° C. and the mixture was stirred for 2 hours and allowed to warm to room temperature. The reaction mixture was adsorbed onto silica and the residue was purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10). The fractions containing the desired product were combined and evaporated under vacuum to give the title product as a colourless foam (0.655 g); 1H NMR Spectrum: (DMSO d6) 1.54-1.78 (m, 2H), 1.91-2.10 (m, 5H), 3.29-3.41 (m, 2H), 3.66-3.76 (m, 1H), 3.78-3.88 (m, 1H), 3.93 (s, 3H), 4.74 (m, 1H), 7.20 (s, 1H), 7.27 (t, 1H), 7.44-7.55 (m, 2H), 7.87 (s, 1H), 836 (s, 1H), 9.54 (s, 1H); Mass Spectrum: (M+H)+ 445.

후처리

  1. temperatureto warm to room temperature
  2. customthe residue was purified by column chromatography
  3. washeluting
  4. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10)
  5. additionThe fractions containing the desired product
  6. customevaporated under vacuum

출처 및 근거

ORD 기록
ord-2ba77dee77024d6b8924cbe612b38089
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399667B2

반응 노트

불러오는 중…