Tetrahydrofuran → HCID 86710079, compound
Reaction equation
[C:1]([C:3]1[CH:8]=[C:7]([CH3:9])[N:6]2[C:10]([CH2:18][CH:19]3[CH2:24][CH2:23][C:22]([F:26])([F:25])[CH2:21][CH2:20]3)=[C:11](C(OCC)=O)[N:12]=[C:5]2[CH:4]=1)#[N:2].[CH3:27][Mg]Br.[Cl-].[NH4+].[CH2:32]1[CH2:36][O:35]CC1>>[F:26][C:22]1([F:25])[CH2:21][CH2:20][CH:19]([CH2:18][C:10]2[N:6]3[C:7]([CH3:9])=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]3=[N:12][C:11]=2[C:36]([OH:35])([CH3:32])[CH3:27])[CH2:24][CH2:23]1Participants
Conditions
- Temperature
- -50 °C
Procedure
Ethyl 7-cyano-3-(4,4-difluorocyclohexylmethyl)-5-methylimidazo[1,2-a]pyridine-2-carboxylate (0.0410 g, 0.113 mmol) obtained in step 3 was dissolved in THF (1.0 mL), and the solution was stirred at −50° C. for 2 hours and then at 0° C. for 30 minutes after adding a THF solution of methylmagnesium bromide (1.1 mol/L) (0.446 mL, 0.500 mmol) at −50° C. Under ice-cooled condition, a saturated ammonium chloride aqueous solution was added to the reaction mixture, and the mixture was filtered through a Presep (registered trademark; diatomaceous earth, granular type M, 4.5 g/25 mL). The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (heptane/ethyl acetate=80/20→65/35) to give 3-(4,4-difluorocyclohexylmethyl)-2-(2-hydroxypropan-2-yl)-5-methylimidazo[1,2-a]pyridine-7-carbonitrile (20.4 mg, yield 52%).
Workup
- temperatureUnder ice-cooled condition
- filtrationthe mixture was filtered through a Presep (registered trademark; diatomaceous earth, granular type M, 4.5 g/25 mL)
- customThe solvent was then evaporated under reduced pressure
- customThe residue was purified by silica gel column chromatography (heptane/ethyl acetate=80/20→65/35)
Sources & evidence
- ORD record
- ord-605478c2b9714077b270baf2bf3ddf57
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09000186B2
Reaction notes
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