Ethyl Acetate → N-(2-Aminophenyl)-4-[3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-1-[3-(4-methylpiperazin-1-yl)propyl]ureidomethyl]benzamide

HRID 658043Notes

Reaction equation

HRID 658043 reaction equation
C(OC(=O)C)C.Cl.C(OC([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[NH:22][C:23](=[O:55])[C:24]1[CH:29]=[CH:28][C:27]([CH2:30][N:31]([CH2:45][CH2:46][CH2:47][N:48]2[CH2:53][CH2:52][N:51]([CH3:54])[CH2:50][CH2:49]2)[C:32]([NH:34][C:35]2[CH:44]=[CH:43][C:38]3[O:39][CH2:40][CH2:41][O:42][C:37]=3[CH:36]=2)=[O:33])=[CH:26][CH:25]=1)=O)(C)(C)C.C(OCC)(=O)C.C(=O)([O-])O.[Na+]>CO>[NH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[NH:22][C:23](=[O:55])[C:24]1[CH:29]=[CH:28][C:27]([CH2:30][N:31]([CH2:45][CH2:46][CH2:47][N:48]2[CH2:53][CH2:52][N:51]([CH3:54])[CH2:50][CH2:49]2)[C:32]([NH:34][C:35]2[CH:44]=[CH:43][C:38]3[O:39][CH2:40][CH2:41][O:42][C:37]=3[CH:36]=2)=[O:33])=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 21866389Hydrogen chloride-ethyl acetateHCID 58000978N-(2-t-Butoxycarbonylaminophenyl)-4-[3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-1-[3-(4-methylpiperazin-1-yl)propyl]ureidomethyl]benzamide

Product 1

HCID 58001268N-(2-Aminophenyl)-4-[3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-1-[3-(4-methylpiperazin-1-yl)propyl]ureidomethyl]benzamideYield 82%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4.0 M hydrogen chloride ethyl acetate solution (10 mL) was added to a solution of N-(2-t-butoxycarbonylaminophenyl)-4-[3-(2,3-dihydrobenz o[1,4]dioxin-6-yl)-1-[3-(4-methylpiperazine-1-yl)propyl]ureidomethyl]benzamide (Reference Compound No. 13-1, 450 mg, 0.68 mmol) in a mixed solvent (ethyl acetate (10 mL) and methanol (10 mL)), and then the mixture was stirred at room temperature for 2.5 hours. Saturated aqueous sodium hydrogen carbonate solution (150 mL) was added thereto, the whole was extracted with chloroform (150 mL), and then the organic layer was washed with brine (150 mL). The organic layer was dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH-modified silica gel, chloroform-methanol) to give 310 mg of the title compound as a colorless amorphous product. (Yield 82%)

Workup

  1. extractionthe whole was extracted with chloroform (150 mL)
  2. washthe organic layer was washed with brine (150 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (NH-modified silica gel, chloroform-methanol)

Sources & evidence

ORD record
ord-6b293b65c8e14d3f87e962ac82638422
Source dataset
uspto-grants-2011_12
Patent number
US08076332B2

Reaction notes

Loading…