Bromomethylcyclopropane → 4-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-(cyclopropylmethyl)piperidine-4-carboxamide

HRID 1867722Notes

Reaction equation

CCN(C(C)C)C(C)C.[CH:10]1([CH2:13]Br)[CH2:12][CH2:11]1.Cl.[Cl:16][C:17]1[C:18]([F:48])=[C:19]([NH:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:46][CH3:47])=[C:31]([CH2:34][N:35]([CH3:45])[C:36]4([C:42]([NH2:44])=[O:43])[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]4)[CH:32]=3)[N:27]=[CH:26][N:25]=2)[CH:20]=[CH:21][CH:22]=1>CN(C)C=O>[Cl:16][C:17]1[C:18]([F:48])=[C:19]([NH:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:46][CH3:47])=[C:31]([CH2:34][N:35]([CH3:45])[C:36]4([C:42]([NH2:44])=[O:43])[CH2:41][CH2:40][N:39]([CH2:13][CH:10]5[CH2:12][CH2:11]5)[CH2:38][CH2:37]4)[CH:32]=3)[N:27]=[CH:26][N:25]=2)[CH:20]=[CH:21][CH:22]=1

Participants

Conditions

Temperature: 100 °C

Procedure

DIPEA (0.068 g, 0.522 mmol) and cyclopropylmethylbromide (0.035 g, 0.260 mmol) were added to a stirred solution of 4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-c arboxamide hydrochloride (0.10 g, 0.172 mmol) in dimethylformamide (1 ml). The reaction mixture was heated at 100° C. for 5 hours, cooled to room temperature and purified by preparative LCMS (standard acidic system) to give the title product (0.0253 g, 27.8%) as a white solid; 1H NMR Spectrum: (DMSO-d6) 0.00 (m, 2H), 0.41 (m, 2H), 0.76 (m, 1H), 1.77 (m, 2H), 2.03-2.13 (m, 7H), 2.81 (m, 2H), 3.32 (m, 2H), 3.61 (s, 2H), 3.91 (s, 3H), 7.06 (s, 1H), 7.14 (s, 2H), 7.26 (t, 1H), 7.47-7.53 (m, 2H), 8.32 (s, 1H), 8.38 (s, 1H), 9.70 (s, 1H); Mass Spectrum: (M+H)+ 527.

Workup

temperaturecooled to room temperature
custompurified by preparative LCMS (standard acidic system)

Sources & evidence

ORD record: ord-431dedb37d6249c2880ee81b13a06bfc
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07632840B2

Reaction notes

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