Methanol → methyl 3-[6-[4-(cyclopropylmethyl)piperazin-1-yl]-4-oxoquinazolin-3(4H)-yl]-4-methylbenzoate

HRID 641975Notes

Reaction equation

HRID 641975 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[N:12]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([N:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[CH:19]=2)[N:14]=[CH:13]1.Br[CH2:30][CH:31]1[CH2:33][CH2:32]1.C(=O)([O-])[O-].[K+].[K+].CO>CN(C=O)C.C(OCC)(=O)C>[CH:31]1([CH2:30][N:26]2[CH2:27][CH2:28][N:23]([C:18]3[CH:19]=[C:20]4[C:15](=[CH:16][CH:17]=3)[N:14]=[CH:13][N:12]([C:3]3[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=3[CH3:1])[C:6]([O:8][CH3:9])=[O:7])[C:21]4=[O:22])[CH2:24][CH2:25]2)[CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 81503BromomethylcyclopropaneHCID 68604387methyl 4-methyl-3-(4-oxo-6-piperazin-1-ylquinazolin-3(4H)-yl)benzoate

Product 1

HCID 68603182methyl 3-[6-[4-(cyclopropylmethyl)piperazin-1-yl]-4-oxoquinazolin-3(4H)-yl]-4-methylbenzoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 4-methyl-3-(4-oxo-6-piperazin-1-ylquinazolin-3(4H)-yl)benzoate (1.41 g), (bromomethyl)cyclopropane (0.40 ml), and potassium carbonate (2.1 g) were stirred in DMF (9.4 ml) at 60° C. for 18 hours. The reaction mixture was diluted with ethyl acetate and washed with water (×3). The combined aqueous layers was extracted with EtOAc and the organic layers combined, washed with brine, dried (magnesium sulphate) and concentrated to yield a brown glass. MeOH was added and the resultant solid collected by filtration and washed with ethyl acetate to yield methyl 3-[6-[4-(cyclopropylmethyl)piperazin-1-yl]-4-oxoquinazolin-3(4H)-yl]-4-methylbenzoate as a white solid (0.39 g); NMR Spectrum: (DMSOd6) 0.00 (m, 2H), 0.38 (m, 2H), 0.76 (m, 1H), 2.05 (s, 3H), 2.14 (d, 2H), 2.52 (m, 4H) 3.17 (m, 4H), 3.75 (s, 3H), 7.36 (s, 1H), 7.51 (m, 3H), 7.85 (s, 1H), 7.90 (d, 1H), 7.97 (s, 1H); Mass Spectrum: M+H+ 433.

Workup

  1. washwashed with water (×3)
  2. extractionThe combined aqueous layers was extracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried (magnesium sulphate)
  5. concentrationconcentrated
  6. customto yield a brown glass
  7. filtrationthe resultant solid collected by filtration
  8. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-d8bface71a584bb29739031d23d6994d
Source dataset
uspto-grants-2010_04
Patent number
US07696215B2

Reaction notes

Loading…