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

HRID 631428Notes

Reaction equation

HRID 631428 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].[OH:23][CH2:24][C:25]([C:28]1[O:32][N:31]=[C:30]([NH:33][C:34](=O)[O:35]C2C=CC=CC=2)[CH:29]=1)([CH3:27])[CH3:26].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:34]([NH:33][C:30]2[CH:29]=[C:28]([C:25]([CH3:27])([CH3:26])[CH2:24][OH:23])[O:32][N:31]=2)=[O:35])[CH:20]=[CH:21][CH:22]=1

Participants

4

Reactant 3

HCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 66794275Phenyl 5-(1-hydroxy-2-methylpropan-2-yl)isoxazol-3-ylcarbamateHCID 910382053-(3-Isopropylisoxazol-5-yl)urea

Product 1

HCID 569538721-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1-hydroxy-2-methylpropan-2-yl)isoxazol-3-yl)ureaYield 61%

Procedure

Prepared from 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline from Example 113A (30 mg, 0.10 mmol) and phenyl 5-(1-hydroxy-2-methylpropan-2-yl)isoxazol-3-ylcarbamate from the previous step (41 mg, 0.15 mmol) according to the method described for 14346,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropylisoxazol-5-yl)urea in Example 122B. Purification via preparative TLC eluting with 10% methanol in dichloromethane afforded 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1-hydroxy-2-methylpropan-2-yl)isoxazol-3-yl)urea as a colorless solid (30 mg, 61%). 1H NMR (300 MHz, DMSO-d6) δ 9.57 (brs, 1H), 8.99 (brs, 1H), 8.56 (s, 1H), 7.56-7.58 (m, 2H), 7.38-7.42 (m, 2H), 7.23-7.26 (m, 1H), 6.95-6.98 (m, 1H), 6.49 (s, 1H), 4.95 (brs, 1H), 3.98-3.99 (2×s, 6H), 3.43 (s, 2H), 1.20 (s, 6H); LC-MS (ESI) m/z 480 (M+H)+.

Workup

  1. customPurification via preparative TLC
  2. washeluting with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-d16b60176ce348018920dd2ec026afc8
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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