1,2-Dichloroethane → 5-(2-Fluoro-4-methylphenyl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]nicotinamide 1-oxide
Reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[N+:11]([O-:18])[CH:12]=[C:13]([CH:17]=1)[C:14]([OH:16])=O.[CH3:19][C:20]1[N:24]=[C:23]([C@H:25]([NH2:27])[CH3:26])[O:22][N:21]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[N+:11]([O-:18])[CH:12]=[C:13]([CH:17]=1)[C:14]([NH:27][C@@H:25]([C:23]1[O:22][N:21]=[C:20]([CH3:19])[N:24]=1)[CH3:26])=[O:16]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 5-(2-fluoro-4-methylphenyl)nicotinic acid 1-oxide (22.6 mg, 0.09 mmol) in DMF (0.5 mL) were added hydrochloride salt of (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine (23.8 mg, 0.12 mmol), EDC (26.3 mg, 0.14 mmol), HOBT (15.4 mg, 0.10 mmol) and diisopropylethylamine (64 μL, 0.37 mmol). The mixture was stirred at ambient temperature. After 72 h, the mixture was purified by reverse chromatography (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid) to give the title compound (18.4 mg). HRMS 357.1367 (M+1). 1H NMR (400 MHz, CDCl3): δ 9.02 (s, 1H); 8.73 (d, J=7.6 Hz, 1H); 8.53 (s, 1H); 7.98 (s, 1H); 7.32 (t, J=8.0 Hz, 1H); 7.08 (d, J=8.0 Hz, 1H); 7.02 (d, J=11.8 Hz, 1H); 5.60-5.51 (m, 1H); 2.42 (s, 3H); 2.29 (s, 3H); 1.80 (d, J=7.1 Hz, 3H).
Workup
- customthe mixture was purified by reverse chromatography (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid)
Sources & evidence
- ORD record
- ord-715ba09f4a784a25a8d7d728537c887a
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08598209B2
Reaction notes
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