Potassium Carbonate → HCID 71476306, compound

HRID 1506605Notes

Reaction equation

HRID 1506605 reaction equation
[Cl:1][C:2]1[C:3]([O:12][C:13]2[CH:14]=[N:15][C:16]([C:19]([C:22]3([C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=4[F:32])[CH2:24][O:23]3)([F:21])[F:20])=[CH:17][CH:18]=2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[NH:33]1[CH:37]=[N:36][N:35]=[N:34]1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C(Cl)Cl>[Cl:1][C:2]1[C:3]([O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:20])[C:22]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=3[F:32])([OH:23])[CH2:24][N:33]3[CH:37]=[N:36][N:35]=[N:34]3)=[N:15][CH:14]=2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 86675113HCID 86675113, compoundHCID 178418441HCID 178418441, compound

Product 1

HCID 71476306HCID 71476306, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a magnetically stirred mixture of 3-chloro-2-((6-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-yl)oxy)-5-(trifluoromethyl)pyridine (U) (356 mg, 0.744 mmol) and 1H-tetrazole (62.5 mg, 0.892 mmol) in dry DMSO (3.718 mL) was added potassium carbonate (206 mg, 1.487 mmol) in a dry 25 mL vial under N2 atmosphere. The reaction mixture was stirred at 60° C. overnight, cooled to RT and diluted with ice-cold water/2N HCl and DCM and the layers were separated on a Phase Separator. The aq. layer was extracted again with DCM and the combined organic extracts were evaporated. The crude residue was purified on silica (ISCO, 40 gram column, gradient to 40% EtOAc/Hexanes over 20 minutes) to afford the title compound. Yield=119 mg (27.7%) of a brown glass. 1H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 8.50 (d, J=2.3 Hz, 1H), 8.27 (dd, J=2.1, 0.9 Hz, 1H), 8.05 (d, J=2.0 Hz, 1H), 7.74-7.63 (m, 2H), 7.34 (td, J=8.9, 6.4 Hz, 1H), 7.21 (s, 1H), 6.83-6.72 (m, 1H), 6.72-6.64 (m, 1H), 5.64 (d, J=14.3 Hz, 1H), 5.13 (d, J=14.1 Hz, 1H). 1H-decoupled 19F NMR (376 MHz, CDCl3) δ−61.74 (s), −103.20 (d, J=15.0 Hz), −103.72-−104.09 (m), −107.86 (d, J=10.9 Hz), −110.78 (d, J=45.0 Hz), −111.48 (d, J=45.0 Hz). MS (ESI): m/z 549.1 (M+H)+.

Workup

  1. temperaturecooled to RT
  2. customthe layers were separated on a Phase Separator
  3. extractionThe aq. layer was extracted again with DCM
  4. customthe combined organic extracts were evaporated
  5. customThe crude residue was purified on silica (ISCO, 40 gram column, gradient to 40% EtOAc/Hexanes over 20 minutes)

Sources & evidence

ORD record
ord-278d6b45ecee4d548489981a43f2ebb6
Source dataset
uspto-grants-2015_12
Patent number
US09220265B2

Reaction notes

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