(S)-3-methyl-3-(2-methyl-5-nitro-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione → (S)-3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)-3-methylpiperidine-2,6-dione

HRID 1409616Notes

Reaction equation

HRID 1409616 reaction equation
[CH3:1][C@:2]1([N:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[N+:21]([O-])=O)[N:12]=[C:11]2[CH3:24])[CH2:7][CH2:6][C:5](=[O:8])[NH:4][C:3]1=[O:9]>C(OCC)(=O)C.CO.[Pd].[O-2].[O-2].[Mn+4]>[NH2:21][C:17]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:18]=1[C:19](=[O:20])[N:10]([C@@:2]1([CH3:1])[CH2:7][CH2:6][C:5](=[O:8])[NH:4][C:3]1=[O:9])[C:11]([CH3:24])=[N:12]2

Participants

5

Reactant 1

HCID 66643019(S)-3-methyl-3-(2-methyl-5-nitro-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione

Product 1

HCID 24967955(S)-3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)-3-methylpiperidine-2,6-dioneYield 37%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 178418406HCID 178418406, compoundCatalystHCID 21584119Ethylacetate methanolSolvent

Procedure

A mixture of (S)-3-methyl-3-(2-methyl-5-nitro-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione (0.30 g, 1.0 mmol) and 10% Pd—C (0.2 g, 50% wet), in 200 mL of 3:1 ethyl acetate-methanol was shaken under 50 psi H2 for 45 minutes. The mixture was filtered through Celite, and the solvent was evaporated. The residue was redissolved in 200 mL of 4:1 dichloromethane-acetone, and manganese dioxide (0.20 g, 2.2 mmol) was added. This mixture was stirred for 16 hours. The mixture was filtered through Celite, and the filtrate was evaporated. The residue was chromatographed on silica gel using a dichloromethane-acetonitrile gradient, eluting (S)-3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)-3-methylpiperidine-2,6-dione as a beige solid (0.10 g, 37% yield): HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 ml/min, 240 nm, 20/80 CH3CN/0.1% H3PO4, 1.63 (99.20%); mp 297-299° C.; 1H NMR (DMSO-d6) δ 1.88 (s, 3H, CH3), 2.31-2.36 (m, 1H, CHH), 2.53-2.59 (m, 2H, 2CHH), 2.62 (s, 3H, CH3), 2.71-2.84 (m, 1H, CHH), 6.53-6.56 (m, 2H, Ar), 6.95 (br, 2H, NH2), 7.35 (t, J=8 Hz, 1H, Ar), 10.72 (s, 1H, NH); 13C NMR (DMSO-d6) δ 24.5, 26.3, 28.3, 29.0, 62.2, 104.2, 110.5, 110.8, 135.0, 147.4, 150.4, 152.9, 164.9, 171.5, 173.0; Anal. Calcd for C15H16N4O3: C, 59.99; H, 5.37; N, 18.66. Found: C, 59.61; H, 5.43; N, 18.59.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. customthe solvent was evaporated
  3. dissolutionThe residue was redissolved in 200 mL of 4:1 dichloromethane-acetone
  4. filtrationThe mixture was filtered through Celite
  5. customthe filtrate was evaporated
  6. customThe residue was chromatographed on silica gel using a dichloromethane-acetonitrile gradient

Sources & evidence

ORD record
ord-75d7c6aafcce4f5ead4e17ab817b3cb9
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

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