Dimethylformamide → HCID 86628520, compound

HRID 546786Notes

Reaction equation

HRID 546786 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:8][CH:9]([F:11])[F:10].[CH3:12][C:13]1[N:14]=[CH:15][N:16]([C:18]2[C:19]([OH:45])=[N:20][C:21](/[CH:24]=[CH:25]/[C:26]3[N:44]=[C:29]4[C@H:30]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=5[C:40]([F:43])([F:42])[F:41])[CH2:31][CH2:32][CH2:33][N:28]4[N:27]=3)=[CH:22][CH:23]=2)[CH:17]=1.CN(C=O)C>C(OCC)(=O)C.O>[CH3:12][C:13]1[N:14]=[CH:15][N:16]([C:18]2[CH:23]=[CH:22][C:21](/[CH:24]=[CH:25]/[C:26]3[N:44]=[C:29]4[CH:30]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=5[C:40]([F:42])([F:43])[F:41])[CH2:31][CH2:32][CH2:33][N:28]4[N:27]=3)=[N:20][C:19]=2[O:45][CH2:8][CH:9]([F:11])[F:10])[CH:17]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 1361862-Bromo-1,1-difluoroethaneHCID 178429903HCID 178429903, compound

Product 1

HCID 86628520HCID 86628520, compoundYield 70.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cesium carbonate (83.7 mg) and 2-bromo-1,1-difluoroethane (34.1 mg) were added to a mixture of 3-(4-methyl-1H-imidazol-1-yl)-6-{(E)-2-[8-(2-trifluoromethylphenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl]vinyl}pyridin-2-ol synthesized in Example 344 (100 mg) and DMF (1.2 mL), and the reaction solution was stirred at room temperature for 48 hours. Water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (carrier: Chromatorex NH; elution solvent: heptane:ethyl acetate=4:1→ethyl acetate) to obtain a racemate of the title compound (80 mg). The resulting racemate (80 mg) was separated by CHIRALPAK™ IB manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm, mobile phase: hexane:ethanol=4:6, flow rate: 11 mL/min) to obtain the title optically active compound with a retention time of 14 minutes and positive optical rotation (33 mg) and the title optically active compound with a retention time of 25 minutes and negative optical rotation (35 mg).

Workup

  1. customthe organic layer was separated
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel chromatography (carrier: Chromatorex NH; elution solvent: heptane:ethyl acetate=4:1→ethyl acetate)

Sources & evidence

ORD record
ord-d06113109c2b49299ebadf693e03e786
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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