3-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)aniline → 1-(3-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)phenyl)-3-(3-(2-methoxyethoxy)-5-(trifluoromethyl)phenyl)urea

HRID 631394Notes

Reaction equation

HRID 631394 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][O:16][CH3:17])[N:9]=[CH:8][N:7]=[C:6]2[O:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=1)[NH2:22].[CH3:26][O:27][CH2:28][CH2:29][O:30][C:31]1[CH:32]=[C:33]([NH:41][C:42](=O)[O:43]C2C=CC=CC=2)[CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1>CO.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][O:16][CH3:17])[N:9]=[CH:8][N:7]=[C:6]2[O:18][C:19]1[CH:20]=[C:21]([NH:22][C:42]([NH:41][C:33]2[CH:34]=[C:35]([C:37]([F:39])([F:40])[F:38])[CH:36]=[C:31]([O:30][CH2:29][CH2:28][O:27][CH3:26])[CH:32]=2)=[O:43])[CH:23]=[CH:24][CH:25]=1

Participants

4

Reactant 2

HCID 668758053-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)anilineHCID 66876567Phenyl 3-(2-methoxyethoxy)-5-(trifluoromethyl)phenylcarbamate

Product 1

HCID 582679051-(3-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)phenyl)-3-(3-(2-methoxyethoxy)-5-(trifluoromethyl)phenyl)ureaYield 76%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)aniline from the previous step (102 mg, 0.3 mmol) was reacted with phenyl 3-(2-methoxyethoxy)-5-(trifluoromethyl)phenylcarbamate from Example 117A (160 mg, 0.45 mmol) in the manner described in Example 115C. The final product was purified by column chromatography (25-100% EtOAc/hexanes then 5-10% MeOH/DCM) to give 1-(3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)phenyl)-3-(3-(2-methoxyethoxy)-5-(trifluoromethyl)phenyl)urea (137 mg, 0.23 mmol, 76%). 1H NMR (300 MHz, DMSO-d6) δ 9.10 (s, 1H), 9.04 (s, 1H), 8.56 (s, 1H), 7.61 (s, 1H), 7.57 (s, 1H), 7.49 (s, 1H), 7.45-7.38 (m, 2H), 7.32-7.26 (m, 2H), 6.96 (d, 1H), 6.87 (s, 1H), 4.37-4.31 (m, 2H), 4.19-4.12 (m, 2H), 4.00 (s, 3H), 3.80-3.73 (m, 2H), 3.70-3.63 (m, 2H), 3.36 (s, 3H), 3.31 (s, 3H); LC-MS (ESI) m/z 603 (M+H)+.

Workup

  1. customThe final product was purified by column chromatography (25-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-764e4719758b4d4da282c19f6a0d2398
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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