Triethylamine → 6-(1,1-Dioxo-1lambda~6~,4-thiazinan-4-yl)-4-(4-fluoro-2-methylphenyl)pyridine-3-carbonitrile
Reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[CH3:17])[CH:5]=[C:4]([N:18]2[CH2:23][CH2:22][S:21](=[O:25])(=[O:24])[CH2:20][CH2:19]2)[N:3]=1.C(N(CC)CC)C>[OH-].[OH-].[Pd+2].CN(C=O)C>[C:8]([C:7]1[C:6]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[CH3:17])=[CH:5][C:4]([N:18]2[CH2:23][CH2:22][S:21](=[O:24])(=[O:25])[CH2:20][CH2:19]2)=[N:3][CH:2]=1)#[N:9]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 25 °C
Procedure
A 300-mL Parr bottle charged with crude 2-chloro-3-cyano-4-(4-fluoro-2-methylphenyl)-6-(1,1-dioxo-thiomorpholin-4-yl)pyridine (19.86 g, 52.29 mmol), 10.9 mL (7.94 g, 78.4 mmol, 1.50 equiv) of triethylamine, 220 mg Pd(OH)2 or 1.62 g (1.57 mmol, 3.0 mol %) of 20% palladium hydroxide on carbon [Pearlman's catalyst, 32.2% LOD] and 100 mL of dry DMF. The mixture was stirred at 25° C. and 48.9–43.2 psi of H2 for 25.5 hours. The pressure was vented, and the mixture was filtered through a 5.0 g pad of cellulose. The cellulose pad was washed with 10 mL of DMF. Water (400 mL) was added to the filtrate and the resulting mixture was stirred for 30 minutes. The precipitate was filtered, washed several times with H2O, and dried to afford 17.52 g (97.0%) of 5-cyano-4-(4-fluoro-2-methylphenyl)-2-(1,1-dioxo-thiomorphlin-4-yl)pyridine as a slightly grey solid (97% conversion).
Workup
- filtrationthe mixture was filtered through a 5.0 g pad of cellulose
- washThe cellulose pad was washed with 10 mL of DMF
- additionWater (400 mL) was added to the filtrate
- stirringthe resulting mixture was stirred for 30 minutes
- filtrationThe precipitate was filtered
- washwashed several times with H2O
- customdried
Sources & evidence
- ORD record
- ord-5bc22300e1214353bf0350cf62406f0f
- Source dataset
- uspto-grants-2008_06
- Patent number
- US07384939B2
Reaction notes
Loading…