Water → N-cyclopropyl-3-[6-(2,3-dihydroxy-2-methylpropoxy)-4-oxoquinazolin-3(4H)-yl]-4-methylbenzamide

HRID 2354206Notes

Reaction equation

HRID 2354206 reaction equation
[CH:1]1([NH:4][C:5](=[O:29])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[C:22](=[O:23])[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([O:24][CH2:25][C:26]([CH3:28])=[CH2:27])[CH:20]=4)[N:15]=[CH:14]3)[CH:7]=2)[CH2:3][CH2:2]1.C[N+]1([O-])CCOCC1.S(=O)(O)[O-].[Na+].[OH2:43].CC(C)=O.[OH2:48]>CC(O)(C)C.[Os](=O)(=O)(=O)=O>[CH:1]1([NH:4][C:5](=[O:29])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[C:22](=[O:23])[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([O:24][CH2:25][C:26]([OH:48])([CH3:28])[CH2:27][OH:43])[CH:20]=4)[N:15]=[CH:14]3)[CH:7]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 962WaterHCID 82029Methyl morpholine oxideHCID 18366337Propan-2-one--water (1/1)HCID 23665763Sodium BisulfiteHCID 66918821HCID 66918821, compound

Product 1

HCID 11774562N-cyclopropyl-3-[6-(2,3-dihydroxy-2-methylpropoxy)-4-oxoquinazolin-3(4H)-yl]-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 6386tert-ButanolSolvent

Procedure

To a solution of N-cyclopropyl-4-methyl-3-[6-[(2-methylprop-2-en-1-yl)oxy]-4-oxoquinazolin-3(4H)-yl]benzamide (1.76 g) in acetone/water (4:1, 40 ml) was added N-methylmorpholine-N-oxide (2.1 g) followed by a solution of osmium tetroxide in 2-methyl-2-propanol (2.5% solution, 1.2 ml). After 18 hours sodium bisulfite (0.1 g) was added and the mixture stirred for a further 1 hour. The crude mixture was poured into water (20 ml) and extracted into ethyl acetate (300 ml). The combined organic extracts were washed with brine (100 ml), dried (magnesium sulfate) and concentrated. Purification by preparative HPLC provided N-cyclopropyl-3-[6-(2,3-dihydroxy-2-methylpropoxy)-4-oxoquinazolin-3(4H)-yl]4 methylbenzamide (AZ12197886) (0.5 g); NMR Spectrum: (CDCl3) 0.45 (m, 2H), 0.75 (m, 2H), 1.32 (s, 3H), 1.70 (m, 2H), 2.10 (s, 3H), 2.70 (m, 1H), 3.60 (d, 1H), 3.70 (m, 1H), 3.90 (m, 2H), 6.70 (d, 1H), 7.30 (m, 1H), 7.45 (m, 1H), 7.50 (m, 2H), 7.70 (m, 1H), 7.90 (s, 1H), 7.95 (t, 1H); Mass Spectrum: M+H+ 424. Further elution provided N-cyclopropyl-3-(6-isobutoxy-4-oxoquinazolin-3(4H)-yl)-4-methylbenzamide (AZ12198379) as a clear oil (70 mg); NMR Spectrum (CDCl3) 0.50 (m, 2H), 0.90 (m, 2H), 1.10 (s, 3H), 1.15 (s, 3H), 2.15 (m, 1H), 2.20 (s, 3H), 2.90 (m, 1H), 3.90 (d, 2H), 6.60 (s, 1H), 7.40 (m, 2H), 7.60 (d, 1H), 7.70 (m, 2H), 7.80 (m, 1H), 7.90 (s, 1H); Mass Spectrum M+H+ 392.

Workup

  1. extractionextracted into ethyl acetate (300 ml)
  2. washThe combined organic extracts were washed with brine (100 ml)
  3. dry with materialdried (magnesium sulfate)
  4. concentrationconcentrated
  5. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-4cbe3e6d15f34ad0918c92f65ef5f7e8
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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