Isopropanol → [4-(3-Aminophenyl)-6,7-dimethoxyquinazolin-2-yl]methylamine

HRID 41490Notes

Reaction equation

HRID 41490 reaction equation
Cl[C:2]1[N:11]=[C:10]([C:12]2[CH:13]=[C:14]([NH2:18])[CH:15]=[CH:16][CH:17]=2)[C:9]2[C:4](=[CH:5][C:6]([O:21][CH3:22])=[C:7]([O:19][CH3:20])[CH:8]=2)[N:3]=1.O1CCCC1.C(O)(C)C.[CH3:32][NH2:33]>CO.C(OCC)(=O)C>[NH2:18][C:14]1[CH:13]=[C:12]([C:10]2[C:9]3[C:4](=[CH:5][C:6]([O:21][CH3:22])=[C:7]([O:19][CH3:20])[CH:8]=3)[N:3]=[C:2]([CH2:32][NH2:33])[N:11]=2)[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 6329MethylamineHCID 8028TetrahydrofuranHCID 576095393-(2-Chloro-6,7-dimethoxyquinazolin-4-yl)phenylamine

Product 1

HCID 25196907[4-(3-Aminophenyl)-6,7-dimethoxyquinazolin-2-yl]methylamine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

Fourteen grams of 3-(2-chloro-6,7-dimethoxyquinazolin-4-yl)phenylamine was suspended in 135 mL of a mixed solution consisting of tetrahydrofuran:isopropanol=2:1. To the reaction mixture was added 89 mL of a methylamine solution in methanol, and the reaction mixture was stirred in a pressure-resistant sealed tube reactor at 130° C. for 24 hours. After the reaction mixture was allowed to cool down to room temperature, it was diluted with 300 mL of ethyl acetate and then washed with 300 mL of water. A water layer was extracted with 100 mL of ethyl acetate, and the combined organic layer was washed with 100 mL of brine. The organic layer was separated and was then dried over anhydrous magnesium sulfate. The desiccant was removed by filtration, the organic layer was concentrated to dryness, and the resultant was triturated with a mixed solvent consisting of ethyl acetate:tetrahydrofuran=3:1. The obtained solid was filtrated, and the filtrate was then washed with ethyl acetate, and dried under aeration to yield 10 g of a target product. The filtrate was adsorbed on a 50 g silica gel column, and it was then eluted with a mixed solution consisting of ethyl acetate:methanol=9:1, and the eluent was concentrated to dryness. The residue was triturated with ethyl acetate, and the obtained solid was then filtrated. The solid was washed with diethyl ether, and dried under aeration to yield 1.4 g of a target product. Total yield: 82.9%

Workup

  1. temperatureto cool down to room temperature
  2. washwashed with 300 mL of water
  3. extractionA water layer was extracted with 100 mL of ethyl acetate
  4. washthe combined organic layer was washed with 100 mL of brine
  5. customThe organic layer was separated
  6. dry with materialwas then dried over anhydrous magnesium sulfate
  7. customThe desiccant was removed by filtration
  8. concentrationthe organic layer was concentrated to dryness
  9. customthe resultant was triturated with a mixed solvent
  10. filtrationThe obtained solid was filtrated
  11. washthe filtrate was then washed with ethyl acetate
  12. customdried under aeration

Sources & evidence

ORD record
ord-8e91439d8e88452b9f2f278dccfe02ac
Source dataset
uspto-grants-2013_09
Patent number
US08530654B2

Reaction notes

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