Tetrahydrofuran → tert-butyl 4-(5-fluoro-6-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)piperidine-1-carboxylate
Reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([CH3:9])=[CH:4][C:3]=1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.[O:24]1CCC[CH2:25]1>>[F:8][C:6]1[C:5]([CH3:9])=[CH:4][C:3]2[N:10]([CH:11]3[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH2:16]3)[C:25](=[O:24])[NH:1][C:2]=2[CH:7]=1Participants
Procedure
1,1-Dimethylethyl 4-[(2-amino-4-fluoro-5-methylphenyl)amino]-1-piperidinecarboxylate (D28) (0.88 mmol, 284 mg) in tetrahydrofuran (30 mL) was treated with N,N′-carbonyldiimidazole (0.88 mmol, 141 mg, 1 eq) under argon at room temperature and was stirred at room temperature overnight. The reaction mixture was then concentrated under vacuum and the residue dissolved in THF (5 ml) and stirred for 3 h then heated at 45° C. for 45 min, then N,N′-carbonyldiimidazole (0.44 mmol, 70 mg, 0.5 eq) was added and allowed to react for 40 min. The mixture was concentrated, partitioned between 10% Na2CO3 aqueous solution and ethyl acetate. Organics were dried on MgSO4, concentrated and chromatographed (EtOAc/pet ether) to give the title compound (0.68 mmol, 239 mg, 77% yield). M−H=348.3.
Workup
- concentrationThe reaction mixture was then concentrated under vacuum
- dissolutionthe residue dissolved in THF (5 ml)
- stirringstirred for 3 h
- temperaturethen heated at 45° C. for 45 min
- customto react for 40 min
- concentrationThe mixture was concentrated
- custompartitioned between 10% Na2CO3 aqueous solution and ethyl acetate
- customOrganics were dried on MgSO4
- concentrationconcentrated
- customchromatographed (EtOAc/pet ether)
Sources & evidence
- ORD record
- ord-467d07f7d1b443caa9ba29e98c546a12
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08288412B2
Reaction notes
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