3-(6,7-Dimethoxyquinazolin-4-ylthio)aniline → HCID 44243223, compound

HRID 871786Notes

Reaction equation

HRID 871786 reaction equation
[CH2:1]([C:3]1[CH:7]=[C:6]([NH:8][C:9](=[O:17])OC2C=CC=CC=2)[N:5]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:4]=1)[CH3:2].[CH3:24][O:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][C:35]=1[O:36][CH3:37])[N:32]=[CH:31][N:30]=[C:29]2[S:38][C:39]1[CH:40]=[C:41]([CH:43]=[CH:44][CH:45]=1)[NH2:42]>CS(C)=O.C(OCC)(=O)C>[CH3:24][O:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][C:35]=1[O:36][CH3:37])[N:32]=[CH:31][N:30]=[C:29]2[S:38][C:39]1[CH:40]=[C:41]([NH:42][C:9]([NH:8][C:6]2[N:5]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:4]=[C:3]([CH2:1][CH3:2])[CH:7]=2)=[O:17])[CH:43]=[CH:44][CH:45]=1

Participants

5

Reactant 2

HCID 569536273-(6,7-Dimethoxyquinazolin-4-ylthio)anilineHCID 66877385phenyl 3-ethyl-1-phenyl-1H-pyrazol-5-ylcarbamate

Product 1

HCID 44243223HCID 44243223, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A stirred mixture of phenyl 3-ethyl-1-phenyl-1H-pyrazol-5-ylcarbamate (prepared as described in Example 352A Step 3) (0.15 g, 0.50 mmol) and 3-(6,7-dimethoxyquinazolin-4-ylthio)aniline (prepared as described in Example 115B) (0.16 g, 0.50 mmol) in DMSO (2 mL) was heated at 70° C. for 15 h. After cooling to rt, the reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (2×20 mL). The organic layer was separated, dried over magnesium sulfate, and concentrated under reduced pressure to afford an oil which was recrystallized from diethyl ether. Further purification via preparative silica gel thin-layer chromatography (eluting with a mixture of 8% methanol in dichloromethane containing 0.5% ammonia) afforded 1-(3-(6,7-dimethoxyquinazolin-4-ylthio)phenyl)-3-(3-ethyl-1-phenyl-1H-pyrazol-5-yl)urea (90 mg, 35%) as a colorless solid. 1H NMR (400 MHz, DMSO-d6) δ 9.38 (s, 1H), 8.67 (s, 1H), 8.61 (s, 1H), 7.77 (s, 1H), 7.17-7.53 (m, 10H), 6.30 (s, 1H), 3.98 (s, 6H), 2.56 (m, 2H), 1.19 (m, 3H); LC-MS (ESI) m/z 527 (M+H)+.

Workup

  1. temperatureAfter cooling to rt
  2. washwashed with water (2×20 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto afford an oil which
  7. customwas recrystallized from diethyl ether
  8. customFurther purification via preparative silica gel thin-layer chromatography (
  9. washeluting with a mixture of 8% methanol in dichloromethane containing 0.5% ammonia)

Sources & evidence

ORD record
ord-e998209c919547b6b534cc16138e70af
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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