Acetyl chloride → 1-Acetyl-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide

HRID 1867725노트

반응식

HRID 1867725 반응식
[C:1](Cl)(=[O:3])[CH3:2].Cl.[Cl:6][C:7]1[C:8]([F:38])=[C:9]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:36][CH3:37])=[C:21]([CH2:24][N:25]([CH3:35])[C:26]4([C:32]([NH2:34])=[O:33])[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH:10]=[CH:11][CH:12]=1.C(N(CC)CC)C>ClCCl>[C:1]([N:29]1[CH2:30][CH2:31][C:26]([N:25]([CH2:24][C:21]2[CH:22]=[C:23]3[C:18](=[CH:19][C:20]=2[O:36][CH3:37])[N:17]=[CH:16][N:15]=[C:14]3[NH:13][C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([Cl:6])[C:8]=2[F:38])[CH3:35])([C:32]([NH2:34])=[O:33])[CH2:27][CH2:28]1)(=[O:3])[CH3:2]

참가 물질

5

반응물 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 690487244-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide hydrochloride

생성물 1

HCID 579798211-Acetyl-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide수율 91%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Acetyl chloride (7 μl, 0.094 mmol) was added to a stirred solution of 4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide hydrochloride (0.05 g, 0.085 mmol, prepared as described in Example 64) and triethylamine (53 μl, 0.38 mmol) in dichloromethane (1 ml) at room temperature. The reaction mixture was stirred at room temperature for 1 hour, concentrated and purified by column chromatography on silica eluting with increasingly polar mixtures of dichloromethane/methanol (100/0-90/10) to give the title product (0.039 g, 91%) as a pale yellow solid; 1H NMR Spectrum: (DMSO-d6) 1.75-1.98 (m, 2H), 2.05 (m, 5H), 2.19 (s, 3H), 3.32-3.75 (m, 6H), 3.94 (s, 3H), 7.20 (s, 1H), 7.26 (m, 2H), 7.34 (t, 1H), 7.51-7.57 (m, 2H), 8.38 (s, 1H), 8.46 (s, 1H), 9.80 (s, 1H); Mass Spectrum: (M+H)+ 515.

후처리

  1. concentrationconcentrated
  2. custompurified by column chromatography on silica eluting
  3. temperaturewith increasingly polar mixtures of dichloromethane/methanol (100/0-90/10)

출처 및 근거

ORD 기록
ord-5f417eb7ed9e43b5a9ccd1db2ed236cd
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07632840B2

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