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

HRID 1868238Notes

Reaction equation

[CH3:1][C:2]1O[C:4](=[O:15])[C:5]2[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.Br.[NH2:17][C@@:18]1([CH3:26])[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25].N1C=CN=C1.C1(OP(OC2C=CC=CC=2)OC2C=CC=CC=2)C=CC=CC=1>CN(C=O)C>[CH3:26][C@:18]1([N:17]2[C:4](=[O:15])[C:5]3[C:6](=[CH:8][CH:9]=[CH:10][C:11]=3[N+:12]([O-:14])=[O:13])[N:7]=[C:2]2[CH3:1])[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25]

Participants

Conditions

Temperature: 45 °C

Procedure

A mixture of 2-methyl-5-nitro-4H-benzo[d][1,3]oxazin-4-one (2.0 g, 9.7 mmol), (S)-3-amino-3-methylpiperidine-2,6-dione hydrobromide (2.2 g, 9.7 mmol), imidazole (1.5 g, 21 mmol), and triphenylphosphite (3.7 g, 12 mmol) in DMF (20 mL) was stirred under nitrogen at 45° C. for 40 hours. The mixture was evaporated, and the residue was chromatographed on silica gel using a dichloromethane-acetonitrile gradient. The product eluted at 15% acetonitrile, providing (S)-3-methyl-3-(2-methyl-5-nitro-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione as a yellow solid (0.70 g, 22% yield); 1H NMR (DMSO-d6) δ 1.94 (s, 3H, CH3), 2.35-2.40 (m, 1H, CHH), 2.45-2.59 (m, 2H, 2CHH), 2.71-2.83 (m, 4H, CH3, CHH), 7.75-7.82 (m, 2H, Ar), 7.95 (dd, J=8, 8 Hz, 1H, Ar), 10.86 (s, 1H, NH).

Workup

customThe mixture was evaporated
customthe residue was chromatographed on silica gel using a dichloromethane-acetonitrile gradient
washThe product eluted at 15% acetonitrile

Sources & evidence

ORD record: ord-b82ba438960e4545b118167a3e068f9c
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07635700B2

Reaction notes

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