Diisopropylethylamine → HCID 58267735, compound

HRID 871496Notes

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].C(N(CC)C(C)C)(C)C.[CH3:32][O:33][CH2:34][CH2:35][O:36][C:37]1[CH:38]=[C:39]([NH:47][C:48](=O)[O:49]C2C=CC=CC=2)[CH:40]=[CH:41][C:42]=1[C:43]([F:46])([F:45])[F:44]>C1COCC1.CN(C)C1C=CN=CC=1>[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:48]([NH:47][C:39]2[CH:40]=[CH:41][C:42]([C:43]([F:45])([F:46])[F:44])=[C:37]([O:36][CH2:35][CH2:34][O:33][CH3:32])[CH:38]=2)=[O:49])[CH:20]=[CH:21][CH:22]=1

Participants

Conditions

Temperature: 50 °C

Procedure

As described in Example 113C, 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline from Example 113A (90 mg, 0.3 mmol) in THF (5 mL) was treated with N,N-diisopropylethylamine (78 μl, 0.45 mmol), 4-(dimethylamino)pyridine (4 mg, 0.03 mmol) and phenyl 3-(2-methoxyethoxy)-4-(trifluoromethyl)phenylcarbamate (161 mg, 0.45 mmol). The reaction mixture was heated to 50° C. for 3 h. After removal of the solvent, the crude material was purified by silica gel chromatography (ethyl acetate/dichloromethane 1:1) to afford 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-(2-methoxyethoxy)-4-(trifluoromethyl)phenyl)urea (109.5 mg, 65%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 9.14 (s, 1H), 9.02 (s, 1H), 8.57 (s, 1H), 7.59 (d, 2H), 7.50-7.38 (m, 2H), 7.43-7.38 (m, 2H), 7.27 (d, 1H), 7.04 (d, 1H), 6.96 (d, 1H), 4.17-4.14 (m, 2H), 4.04 (s, 6H), 3.69-3.67 (m, 2H), 3.34 (s, 3H); LC-MS (ESI) m/z 559 (M+H)+.

Workup

customAfter removal of the solvent
customthe crude material was purified by silica gel chromatography (ethyl acetate/dichloromethane 1:1)

Sources & evidence

ORD record: ord-d38ae6f527964195869adcf6d41fd45a
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969587B2

Reaction notes

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