Sodium Hydroxide → HCID 21890843, compound

HRID 721925Notes

Reaction equation

HRID 721925 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](O)=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.Cl[C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH3:29])=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1.[OH-:30].[Na+]>CC(CC)=O.O>[CH3:27][O:26][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][C:22]=1[O:28][CH3:29])[N:19]=[CH:18][N:17]=[C:16]2[O:30][C:2]1[CH:7]=[CH:6][C:5]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 27693644-Chloro-6,7-dimethoxyquinazolineHCID 21889982HCID 21889982, compound

Product 1

HCID 21890843HCID 21890843, compoundYield 113.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6569Methyl Ethyl KetoneSolvent

Procedure

3-Fluoro4-nitrophenol (300 mg), morpholine (800 μl), and calcium carbonate (50 mg) were added to dimethylformamide (3 ml), and the mixture was heated at 130° C. for 12 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give 3-morpholino-4-nitrophenol (400 mg, yield 94%). The resultant 3-morpholino-4-nitrophenol (400 mg) was added to dimethylformamide (3 ml). Palladium hydroxid-carbon (110 mg) and hydrogen were added thereto, and the mixture was stirred at room temperature for 4 hr. The reaction solution was filtered through Celite, and the filtrate was concentrated. The residue was then purified by chromatography on silica gel using chloroform/acetone for development to give 4-amino-3-morpholinophenol (296 mg, yield 85%). The resultant 4-amino-3-morpholinophenol (296 mg), 4-chloro-6,7-dimethoxyquinazoline (479 mg), and n-tetraethylammonium bromide (244 mg) were dissolved in ethyl methyl ketone (10 ml) to prepare a solution. A solution (10 ml) of sodium hydroxide (479 mg) in water was added to the solution, and the mixture was sitrred at 80° C. for 4 hr. Water was added to the reaction solution, and the organic layer was extracted and was concentrated. The residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (396 mg, yield 68%).

Workup

  1. customto prepare a solution
  2. extractionthe organic layer was extracted
  3. concentrationwas concentrated
  4. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-5de554e7f3b843a9a535ffcb999c4f28
Source dataset
uspto-grants-2006_11
Patent number
US07135466B2

Reaction notes

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