1-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropylisoxazol-5-yl)urea → 3-(3-(2-Fluoropropan-2-yl)isoxazol-5-yl)urea

HRID 631509Notes

Reaction equation

HRID 631509 reaction equation
COC1C=C2C(=CC=1OC)N=C[N:7]=C2SC1C=C(C=CC=1)N.[F:23][C:24]([C:27]1[CH:31]=[C:30]([NH:32][C:33](=[O:41])OC2C=CC=CC=2)[O:29][N:28]=1)([CH3:26])[CH3:25].COC1C=C2C(=CC=1OC)N=CN=C2OC1C=C(NC(NC2ON=C(C(C)C)C=2)=O)C=CC=1>>[F:23][C:24]([C:27]1[CH:31]=[C:30]([NH:32][C:33](=[O:41])[NH2:7])[O:29][N:28]=1)([CH3:26])[CH3:25]

Participants

4

Reactant 3

HCID 442434351-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropylisoxazol-5-yl)ureaHCID 569536273-(6,7-Dimethoxyquinazolin-4-ylthio)anilineHCID 66876626Phenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamate

Product 1

HCID 1317354183-(3-(2-Fluoropropan-2-yl)isoxazol-5-yl)ureaYield 118.7%

Procedure

3-(6,7-dimethoxyquinazolin-4-ylthio)aniline from Example 115B (200 mg, 0.639 mmol) was reacted with phenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamate from Example 42A (253 mg, 0.959 mmol) according to the method described for 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropylisoxazol-5-yl)urea in Example 122B, except the reaction mixture was stirred at room temperature for 72 h. Purification via trituration with methanol afforded 14346,7-dimethoxyquinazolin-4-ylthio)phenyl)-3-(3-(2-fluoropropan-2-yl)isoxazol-5-yl)urea as a colorless solid (142 mg, 46%). 1H NMR (300 MHz, DMSO-d6) δ 10.43 (brs, 1H), 9.13 (brs, 1H), 8.70 (s, 1H), 7.84 (s, 1H), 7.57 (m, 1H), 7.46 (m, 1H), 7.30-7.35 (m, 3H), 6.16 (s, 1H), 3.99 (s, 6H), 1.67 (d, J=21 Hz, 6H); LC-MS (ESI) m/z 484 (M+H)+.

Workup

  1. customPurification via trituration with methanol

Sources & evidence

ORD record
ord-f20dfcffa6f149dcb8b473d0ba64e2fb
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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