Dimethylacetamide → 6-Amino-2-(trifluoromethyl)pyridine-3-carbonitrile
Reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH2:12])=[N:6][C:7]=1[C:8]([F:11])([F:10])[F:9].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C[C:56]([N:58](C)C)=O>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:12][C:5]1[CH:4]=[CH:3][C:2]([C:56]#[N:58])=[C:7]([C:8]([F:11])([F:10])[F:9])[N:6]=1Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 160 °C
Procedure
A mixture of 5-bromo-6-(trifluoromethyl)pyridin-2-amine (3.0 g, 12.3 mmol), Zn(CN)2 (0.81 g, 6.9 mmol), Pd2(dba)3 (0.57 g, 0.6 mmol), and Xantphos (0.72 g, 1.2 mmol) in DMA (12 mL) was placed in a sealed tube. The mixture was degassed with argon and stirred at 160° C. for 20 h. The mixture was poured into water and extracted with EtOAc (2×). The combined organic layers were dried over magnesium sulfate and concentrated to dryness. The residue was purified by column chromatography on silica gel eluting with 3:1 EtOAc/hexanes to afford 1.9 g of 6-amino-2-(trifluoromethyl)nicotinonitrile as a solid. 1H NMR (400 MHz, CDCl3) δ 7.74 (d, 1H), 6.67 (d, 1H).
Workup
- customwas placed in a sealed tube
- customThe mixture was degassed with argon
- additionThe mixture was poured into water
- extractionextracted with EtOAc (2×)
- dry with materialThe combined organic layers were dried over magnesium sulfate
- concentrationconcentrated to dryness
- customThe residue was purified by column chromatography on silica gel eluting with 3:1 EtOAc/hexanes
Sources & evidence
- ORD record
- ord-dc3f96731b004ba48ecbbfd08e569727
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09108944B2
Reaction notes
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