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

HRID 1867725Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1867725
[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]

Komponenten

5

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-5f417eb7ed9e43b5a9ccd1db2ed236cd
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07632840B2

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