Triethylamine → N-(1-(2-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)azetidin-3-yl)acetamide

HRID 591772Notes

Reaction equation

HRID 591772 reaction equation
[NH:1]1[CH2:4][CH:3]([NH:5][C:6](=[O:8])[CH3:7])[CH2:2]1.Br[CH2:10][CH2:11][O:12][C:13]1[C:18]([CH3:19])=[CH:17][C:16]([C:20]2[NH:29][C:28](=[O:30])[C:27]3[C:22](=[CH:23][C:24]([O:33][CH3:34])=[CH:25][C:26]=3[O:31][CH3:32])[N:21]=2)=[CH:15][C:14]=1[CH3:35].C(N(CC)CC)C>CN(C=O)C>[CH3:32][O:31][C:26]1[CH:25]=[C:24]([O:33][CH3:34])[CH:23]=[C:22]2[C:27]=1[C:28](=[O:30])[NH:29][C:20]([C:16]1[CH:17]=[C:18]([CH3:19])[C:13]([O:12][CH2:11][CH2:10][N:1]3[CH2:4][CH:3]([NH:5][C:6](=[O:8])[CH3:7])[CH2:2]3)=[C:14]([CH3:35])[CH:15]=1)=[N:21]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 13401968N-(azetidin-3-yl)acetamideHCID 1364005142-[4-(2-bromoethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-3H-quinazolin-4-one

Product 1

HCID 136348037N-(1-(2-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)azetidin-3-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of N-azetidin-3-yl-acetamide (0.30 g crude, 1.99 mmol) and 2-[4-(2-bromo-ethoxy)-3,5-dimethyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one (0.43 g, 1.00 mmol) in anhydrous DMF (10 mL) was added triethylamine (3 mL). The reaction mixture was stirred at room temperature for 3 days under nitrogen. Solvent was evaporated under reduced pressure, water (50 mL) was added, and the precipitated solid was filtered. The aqueous phase was extracted with ethyl acetate (2×100 mL). The organic phase was dried over anhydrous Na2SO4. Solvent was evaporated, and crude compound was purified by the Simpliflash system (0-5% 7 N ammonia in methanol and CH2Cl2 as eluent) to give the title compound as a white solid. Yield: 0.30 g (63%). MP 111.8-113.6° C. 1H NMR (400 MHz, CDCl3): δ 9.60 (br s, 1H), 7.69 (s, 2H), 6.82 (d, J=2.34 Hz, 1H), 6.46 (d, J=2.34 Hz, 1H), 6.10 (d, J=7.81 Hz, 1H), 4.71-4.44 (m, 1H), 3.97 (s, 3H), 3.93 (s, 3H), 3.85-3.67 (m, 4H), 3.26-3.13 (m, 2H), 2.90 (t, J=5.46 Hz, 2H), 2.36 (s, 6H), 2.01 (s, 3H). MS (ES+) m/z: 467.20 (M+1).

Workup

  1. customSolvent was evaporated under reduced pressure, water (50 mL)
  2. additionwas added
  3. filtrationthe precipitated solid was filtered
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×100 mL)
  5. dry with materialThe organic phase was dried over anhydrous Na2SO4
  6. customSolvent was evaporated
  7. customcrude compound was purified by the Simpliflash system (0-5% 7 N ammonia in methanol and CH2Cl2 as eluent)

Sources & evidence

ORD record
ord-6ba2e69356644867a021d531496af9cb
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

Loading…