Hydrochloric Acid → N-(3-chloro-2-fluorophenyl)-7-methoxy-6-(piperidin-4-yloxy)quinazolin-4-amine

HRID 857948Notes

Reaction equation

Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:27][CH3:28])=[C:10]([O:13][CH:14]3[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]3)[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(O)(C)C>[NH:17]1[CH2:16][CH2:15][CH:14]([O:13][C:10]2[CH:11]=[C:12]3[C:7](=[CH:8][C:9]=2[O:27][CH3:28])[N:6]=[CH:5][N:4]=[C:3]3[NH:33][C:32]2[CH:34]=[CH:35][CH:36]=[C:30]([Cl:29])[C:31]=2[F:37])[CH2:19][CH2:18]1

Participants

Conditions

Temperature: 100 °C

Procedure

4.0M HCl in Dioxane (4.0 ml) was added to a suspension of tert-butyl 4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1-carboxylate (2.62 g) and 3-chloro-2-fluoroaniline (1.08 g) in iso-propanol (50 ml). The reaction mixture was stirred and heated at 100° C. for 2 hours. The yellow precipitate was filtered hot and washed with iso-propanol followed by diethylether and dried under vacuum to give 6-(piperidin-4-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline as a di-hydrochloride salt (2.38 g); 1H NMR Spectrum: (DMSO d6) 1.84–1.99 (m, 2H), 2.22–2.33 (m, 2H), 3.12–3.33 (m, 4H), 4.00 (s, 3H), 5.08 (m, 1H), 7.34 (t, 1H), 7.40 (s, 1H), 7.50 (t, 1H), 7.62 (t, 1H), 8.80 (s, 1H), 8.84–8.94 (m, 2H), 8.99–9.11 (m, 1H); Mass Spectrum: (M+H)+ 403.

Workup

filtrationThe yellow precipitate was filtered hot
washwashed with iso-propanol
customdried under vacuum

Sources & evidence

ORD record: ord-37073293ab0f4f9386946bbdf8785a93
Source dataset: uspto-grants-2006_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07148230B2

Reaction notes

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