Sodium hydride → HCID 44243396, compound

HRID 631336Notes

Reaction equation

HRID 631336 reaction equation
[H-].[Na+].[C:3]([C:7]1[O:11][N:10]=[C:9]([NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([SH:22])[CH:17]=2)=[O:14])[CH:8]=1)([CH3:6])([CH3:5])[CH3:4].[Cl:23][C:24]1[N:33]=[C:32](Cl)[C:31]2[C:26](=[CH:27][C:28]([O:37][CH3:38])=[C:29]([O:35][CH3:36])[CH:30]=2)[N:25]=1>CN(C=O)C.O>[C:3]([C:7]1[O:11][N:10]=[C:9]([NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([S:22][C:32]3[C:31]4[C:26](=[CH:27][C:28]([O:37][CH3:38])=[C:29]([O:35][CH3:36])[CH:30]=4)[N:25]=[C:24]([Cl:23])[N:33]=3)[CH:17]=2)=[O:14])[CH:8]=1)([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 5203272,4-Dichloro-6,7-dimethoxyquinazolineHCID 668758091-(5-Tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea

Product 1

HCID 44243396HCID 44243396, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a slurry of sodium hydride (7.5 mg, 0.3 mmol) in DMF (3 mL) was added 1-(5-tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea described in Example 44A (90 mg, 0.3 mmol), and the solution stirred at room temperature When gas evolution ceased, 2,4-dichloro-6,7-dimethoxyquinazoline (78 mg, 0.3 mmol) was added and the solution heated at 50° C. overnight, cooled to room temperature, and diluted with H2O. The mixture was extracted with EtOAc, the organic layer washed with aqueous sat. NaHCO3 and brine, dried over MgSO4, filtered and concentrated in vacuo. The crude solid was purified by HPLC to give 1-(5-tert-butylisoxazol-3-yl)-3-(3-(2-chloro-6,7-dimethoxyquinazolin-4-ylthio)phenyl)urea (20 mg, 0.04 mmol, 13%). 1H NMR (300 MHz, DMSO-d6) δ 9.79 (s, 1H), 9.53 (s, 1H), 7.90 (s, 1H), 7.62 (d, 1H), 7.44 (t, 1H), 7.36 (s, 2H), 7.27 (d, 1H), 6.49 (s, 1H), 4.00 (s, 6H), 1.28 (s, 9H); LC-MS (ESI) m/z 514 (M+H)+.

Workup

  1. temperaturethe solution heated at 50° C. overnight
  2. temperaturecooled to room temperature
  3. extractionThe mixture was extracted with EtOAc
  4. washthe organic layer washed with aqueous sat. NaHCO3 and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude solid was purified by HPLC

Sources & evidence

ORD record
ord-cc018384ea1e4dda9bddd6d9e2ccc673
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

Loading…