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

HRID 641982Notes

Reaction equation

HRID 641982 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.[C:29]1(=O)[CH2:32][CH2:31][CH2:30]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH:32]1([CH2:29][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)[CH2:30][CH2:31]1

Participants

7

Reactant 4

HCID 962WaterHCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 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 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-methyl-3-(4-oxo-6-piperazin-1-ylquinazolin-3(4H)-yl)benzoate (0.5 g) and cyclobutanone (0.20 ml) in THF (42.5 ml) was added titanium (IV) isopropoxide (0.75 ml) and the solution stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (0.83 g) was added and the reaction stirred at room temperature for 18 hours. Water was added and the resultant solid removed by filtration. The aqueous filtrate was washed with ethyl acetate. The organic layer was washed 1N NaOH (×2), water, brine, dried (magnesium sulphate) and to yield methyl 3-[6-[4-(cyclopropylmethyl)piperazin-1-yl]-4-oxoquinazolin-3(4H)-yl]-4-methylbenzoate as a yellow foam (0.45 g); NMR Spectrum: (DMSOd6) 1.66 (m, 2H), 1.84 (m, 2H), 2.00 m, 2H), 2.16 (s, 3H), 2.42 (m, 4H), 2.75 (m, 1H), 3.27 (m, 4H), 3.87 (s, 3H), 7.48 (s, 1H), 7.62 (m, 3H), 7.97 (s, 1H), 8.02 (d, 1H), 8.09 (s, 1H); Mass Spectrum: M+H+ 433.

Workup

  1. stirringthe reaction stirred at room temperature for 18 hours
  2. customthe resultant solid removed by filtration
  3. washThe aqueous filtrate was washed with ethyl acetate
  4. washThe organic layer was washed 1N NaOH (×2), water, brine
  5. dry with materialdried (magnesium sulphate)

Sources & evidence

ORD record
ord-b66f83daba6d4472b2b66ec864a7f6fb
Source dataset
uspto-grants-2010_04
Patent number
US07696215B2

Reaction notes

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