3-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline → 1-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-(2-fluoropropan-2-yl)isoxazol-5-yl)urea

HRID 631413Notes

Reaction equation

HRID 631413 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].[F:23][C:24]([C:27]1[CH:31]=[C:30]([NH:32][C:33](=O)[O:34]C2C=CC=CC=2)[O:29][N:28]=1)([CH3:26])[CH3:25].C(C1C=C(NC(=O)N)ON=1)(C)C>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:17]=[C:18]([NH:19][C:33]([NH:32][C:30]2[O:29][N:28]=[C:27]([C:24]([F:23])([CH3:25])[CH3:26])[CH:31]=2)=[O:34])[CH:20]=[CH:21][CH:22]=1

Participants

4

Reactant 3

HCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 66876626Phenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamateHCID 910382053-(3-Isopropylisoxazol-5-yl)urea

Product 1

HCID 442434721-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-(2-fluoropropan-2-yl)isoxazol-5-yl)ureaYield 45%

Procedure

3-(6,7-dimethoxyquinazolin-4-yloxy)aniline from Example 113A (89 mg, 0.3 mmol) and phenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamate from Example 42A (95 mg, 0.36 mmol) were reacted according to the method described for 143-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropylisoxazol-5-yl)urea in Example 122B to afford 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-(2-fluoropropan-2-yl)isoxazol-5-yl)urea as a colorless solid (63 mg, 45%). 1H NMR (300 MHz, DMSO-d6) δ 10.50 (brs, 1H), 9.15 (s, 1H), 8.56 (s, 1H), 7.57-7.58 (m, 2H), 7.40-7.45 (m, 2H), 7.32 (m, 1H), 7.00 (m, 1H), 6.14 (s, 1H), 3.99-4.00 (2×s, 6H), 1.67 (d, J=21 Hz, 6H); LC-MS (ESI) m/z 468 (M+H)+.

Sources & evidence

ORD record
ord-cca13e7f58ad48849d41ee6008ec4697
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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