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

HRID 1948906Notes

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-0b16b6752a324c16bd0d957ade373e31
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399667B2

Reaction notes

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