Potassium Carbonate → 1-(2,4-Difluoro-benzyl)-6-[4-(6-ethoxy-5-trifluoromethyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile

HRID 906860Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:7]2[N:12]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[F:21])[C:11](=[O:22])[C:10]([C:23]#[N:24])=[C:9]([C:25]([F:28])([F:27])[F:26])[CH:8]=2)[O:5][CH:6]=1.[CH2:29]([O:31][C:32]1[C:37]([C:38]([F:41])([F:40])[F:39])=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][N:33]=1)[CH3:30].C(OC1C(C(F)(F)F)=CC(B(O)O)=CN=1)C.C(=O)([O-])[O-].[K+].[K+]>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.COCCOC.O>[F:21][C:15]1[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=1[CH2:13][N:12]1[C:7]([C:4]2[O:5][CH:6]=[C:2]([C:35]3[CH:34]=[N:33][C:32]([O:31][CH2:29][CH3:30])=[C:37]([C:38]([F:41])([F:40])[F:39])[CH:36]=3)[CH:3]=2)=[CH:8][C:9]([C:25]([F:28])([F:27])[F:26])=[C:10]([C:23]#[N:24])[C:11]1=[O:22]

Participants

Conditions

Temperature: 80 °C

Procedure

6-(4-Bromo-furan-2-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile (98 mg, 0.22 mmol), 2-ethoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridine (125 mg, 0.54 mmol) (or corresponding 2-ethoxy-3-trifluoromethylpyridine-5-boronic acid), potassium carbonate (149 mg, 1.08 mmol), and tetrakis(triphenylphosphine)palladium (0) (25 mg, 0.1 mmol) were mixed with 2.5 ml 9:1 DME/H2O (v/v), then heated at 80° C. overnight. All solvent was removed in vacuo. The crude product was purified by column chromatography on silica gel (10→30% EtOAC/Hexane, 0.25% Et3N in hexane) to give 1-(2,4-difluoro-benzyl)-6-[4-(6-ethoxy-5-trifluoromethyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile as a yellow solid (29 mg, 37% yield). 1H-NMR (400 MHz, CDCl3): δ 1.45 (t, 3H, J=7.07), 4.53 (q, 2H, J=7.07), 5.58 (s, 2H), 6.83 (s, 1H), 6.84 (m, 1H), 6.87 (m, 1H), 7.04 (d, 1H, J=0.76), 7.13 (m, 1H), 7.87 (d, 1H, J=2.27), 7.90 (d, 1H, J=0.76), 8.38 (d, 1H, J=2.27).

Workup

customAll solvent was removed in vacuo
customThe crude product was purified by column chromatography on silica gel (10→30% EtOAC/Hexane, 0.25% Et3N in hexane)

Sources & evidence

ORD record: ord-888760933bc6421db348c7030b4b9e49
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08013001B2

Reaction notes

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