3-(6-Ethoxy-7-methoxyquinazolin-4-ylthio)aniline → 1-(3-(6-Ethoxy-7-methoxyquinazolin-4-ylthio)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea

HRID 631582Notes

Reaction equation

HRID 631582 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[CH:9][N:8]=[C:7]2[S:16][C:17]1[CH:18]=[C:19]([CH:21]=[CH:22][CH:23]=1)[NH2:20])[CH3:2].[F:24][C:25]([F:45])([F:44])[C:26]([C:29]1[O:33][N:32]=[C:31]([NH:34][C:35](=O)[O:36]C2C=CC=CC=2)[CH:30]=1)([CH3:28])[CH3:27]>C1COCC1.CN(C)C1C=CN=CC=1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[CH:9][N:8]=[C:7]2[S:16][C:17]1[CH:18]=[C:19]([NH:20][C:35]([NH:34][C:31]2[CH:30]=[C:29]([C:26]([CH3:28])([CH3:27])[C:25]([F:45])([F:44])[F:24])[O:33][N:32]=2)=[O:36])[CH:21]=[CH:22][CH:23]=1)[CH3:2]

Participants

5

Reactant 2

HCID 668767623-(6-Ethoxy-7-methoxyquinazolin-4-ylthio)anilineHCID 66877298[5-(2,2,2-Trifluoro-1,1-dimethyl-ethyl)-isoxazol-3-yl]-carbamic acid phenyl ester

Product 1

HCID 582678011-(3-(6-Ethoxy-7-methoxyquinazolin-4-ylthio)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)ureaYield 21%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-(6-ethoxy-7-methoxyquinazolin-4-ylthio)aniline (100 mg, 0.305 mmol) and phenyl 5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-ylcarbamate described in Example 260A (144 mg, 0.458 mmol) in anhydrous THF (5 mL), was added 4-(dimethylamino)pyridine (6 mg, 0.0492 mmol) and the mixture was stirred at rt for 15 h. Concentration in vacuo followed by purification via silica gel column chromatography (eluted with a gradient of 20% ethyl acetate in hexanes to 100% ethyl acetate), afforded 1-(3-(6-ethoxy-7-methoxyquinazolin-4-ylthio)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea (35 mg, 21%) as a colorless solid. 1H NMR (300 MHz, DMSO-d6) δ 9.74 (brs, 1H), 9.02 (s, 1H), 8.69 (s, 1H), 7.85 (m, 1H), 7.28-7.51 (m, 5H), 6.88 (s, 1H), 4.23 (q, J=7 Hz, 2H), 3.99 (s, 3H), 1.54 (s, 6H), 1.45 (t, J=7 Hz, 3H); LC-MS (ESI) m/z 548 (M+H)+.

Workup

  1. concentrationConcentration in vacuo
  2. customfollowed by purification via silica gel column chromatography (
  3. washeluted with a gradient of 20% ethyl acetate in hexanes to 100% ethyl acetate),

Sources & evidence

ORD record
ord-cd23198d944045d9beb36ec2d2b10b0a
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

Loading…