Hydrochloric Acid → HCID 68908613, compound

HRID 2099375Notes

Reaction equation

Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][C@H:16]3[CH2:21][CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17]3)=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:29][C:30]1[C:31]([F:37])=[C:32]([CH:34]=[CH:35][CH:36]=1)[NH2:33]>O1CCOCC1.C(#N)C>[ClH:2].[ClH:29].[Cl:29][C:30]1[C:31]([F:37])=[C:32]([NH:33][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:15][C@H:16]4[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]4)=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[CH:5][N:4]=2)[CH:34]=[CH:35][CH:36]=1

Participants

Conditions

Temperature: 80 °C

Procedure

4.0M HCl in dioxane (6.0 ml) was added to a stirred suspension of tert-butyl (3S)-3-[(4-chloro-6-methoxyquinazolin-7-yl)oxy]piperidine-1-carboxylate (3.21 g) and 3-chloro-2-fluoroaniline (0.98 ml) in acetonitrile (50 mL). The reaction mixture was heated at 80° C. and left at this temperature overnight. The solvent was evaporated and the residue purified by flash column chromatography eluting with increasingly polar mixtures of methylene chloride/7N ammonia solution in methanol (97/3 to 95/5) to give N-(3-chloro-2-fluorophenyl)-6-methoxy-7-[(3S)-piperidin-3-yloxy]quinazolin-4-amine dihydrochloride as a solid (3.20 g); 1H NMR Spectrum: (DMSO d6) 1.56 (m, 2H), 1.72 (m, 1H), 2.12 (m, 1H), 2.48-2.59 (m, 2H), 2.82 (m,1H), 3.20 (m, 1H), 3.95 (s, 3H), 4.49 (m, 1H), 7.26 (s, 1H), 7.28 (m, 1H), 7.47 (m, 1H), 7.53 (m, 1H), 7.81 (s, 1H), 8.38 (s, 1H), 9.63(s, 1H); Mass Spectrum: (M+H)+ 403.

Workup

customThe solvent was evaporated
customthe residue purified by flash column chromatography
washeluting
temperaturewith increasingly polar mixtures of methylene chloride/7N ammonia solution in methanol (97/3 to 95/5)

Sources & evidence

ORD record: ord-a4c596b4e26446e283f994cf6a196a16
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07569577B2

Reaction notes

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