Formaldehyde → Vandetanib

HRID 346547

Reaction equation

C=O.[Br:3][C:4]1[CH:37]=[CH:36][C:7]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH:23]4[CH2:28][CH2:27][N:26]([C:29](OC(C)(C)C)=O)[CH2:25][CH2:24]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[C:6]([F:38])[CH:5]=1>C(O)=O>[Br:3][C:4]1[CH:37]=[CH:36][C:7]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH:23]4[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[C:6]([F:38])[CH:5]=1

Participants

Conditions

Temperature: 95 °C

Procedure

37% Aqueous formaldehyde (3.5 ml, 42 mmol) was added to a solution of 4-(4-bromo-2-fluoroanilino)-7-(1-(tert-butoxycarbonyl)piperidin-4-ylmethoxy)-6-methoxyquinazoline (3.49 g, 6.22 mmol), (prepared as described for the starting material in Example 1), in formic acid (35 ml). After heating at 95° C. for 4 hours the volatiles were removed under vacuum. The residue was suspended in water and the mixture was adjusted to pH 10.5 by slow addition of a solution of 2N sodium hydroxide. The suspension was extracted with ethyl acetate. The organic layer was washed with brine, dried MgSO4 and evaporated to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (2.61 g, 88%).

Workup

custom(prepared
customwere removed under vacuum
additionthe mixture was adjusted to pH 10.5 by slow addition of a solution of 2N sodium hydroxide
extractionThe suspension was extracted with ethyl acetate
washThe organic layer was washed with brine, dried MgSO4
customevaporated

Sources & evidence

ORD record: ord-9fc48b1154c74828a455032b889f2591
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07173038B1

Linked notes

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