Dimethylformamide → (S)-5-Cyano-N-((3-fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)-methyl)-6-oxo-1,6-dihydropyridine-3-carboxamide

HRID 509361Notes

Reaction equation

HRID 509361 reaction equation
Br[C:2]1[C:7](=[O:8])[NH:6][CH:5]=[C:4]([C:9]([NH:11][C@H:12]([C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][N:24]=2)[C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)=[O:10])[CH:3]=1.[CH3:30][N:31](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:30]([C:2]1[C:7](=[O:8])[NH:6][CH:5]=[C:4]([C:9]([NH:11][C@H:12]([C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][N:24]=2)[C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:20])[F:22])=[CH:15][CH:14]=2)=[O:10])[CH:3]=1)#[N:31]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 71144085(S)-5-Bromo-N-((3-fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)-methyl)-6-oxo-1,6-dihydropyridine-3-carboxamide

Product 1

HCID 71144140(S)-5-Cyano-N-((3-fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)-methyl)-6-oxo-1,6-dihydropyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

To a solution of (S)-5-bromo-N-((3-fluoropyridin-2-yl)(4-(trifluoro-methyl)phenyl)methyl)-6-oxo-1,6-dihydropyridine-3-carboxamide (0.080 g, 0.170 mmol) in DMF (0.5 mL) was added zinc(II) cyanide (0.043 mL, 0.681 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.020 g, 0.017 mmol). The resulting mixture was then subjected to a microwave irradiation at 130° C. for 30 min. Then, the mixture was purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give the title compound as a white solid. 1H NMR (400 MHz, MeOH) δ ppm 8.63 (d, J=2.5 Hz, 1H), 8.51 (d, J=4.7 Hz, 1H), 8.42 (d, J=2.5 Hz, 1H), 7.55-7.73 (m, 6H), 7.47 (dt, J=8.5, 4.4 Hz, 1H), 6.75 (s, 1H). MS (ESI pos. ion) m/z: 417.0 (M+H).

Workup

  1. customThe resulting mixture was then subjected to a microwave irradiation at 130° C. for 30 min
  2. customThen, the mixture was purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA)

Sources & evidence

ORD record
ord-564b920f65c54e1a930335535350045d
Source dataset
uspto-grants-2015_08
Patent number
US09096527B2

Reaction notes

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