Dimethyl Sulfoxide → HCID 178496639, compound

HRID 81194Notes

Reaction equation

HRID 81194 reaction equation
Br[C:2]1[N:19]([CH2:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]2)[C:5]2[C:6]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=3)=[N:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=2[N:3]=1.[F-].[K+].CS(C)=[O:32].CC[N:36]([CH:40]([CH3:42])[CH3:41])[CH:37]([CH3:39])C.[C:43](OCC)(=[O:45])C>>[Cl:18][C:16]1[CH:17]=[C:12]([C:6]2[C:5]3[N:19]([CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]4)[C:2]([N:36]4[CH2:37][C@H:39]([O:45][CH3:43])[CH2:42][C@H:40]4[CH2:41][OH:32])=[N:3][C:4]=3[CH:9]=[C:8]([C:10]#[N:11])[N:7]=2)[CH:13]=[N:14][CH:15]=1

Participants

6

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 178461197HCID 178461197, compound

Product 1

HCID 178496639HCID 178496639, compound

Conditions

Temperature
100 °C

Procedure

To a vial were added ((2S,4R)-4-methoxypyrrolidin-2-yl)methanol, HCl (0.303 g, 1.81 mmol), 2-bromo-4-(5-chloropyridin-3-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1) (0.805 g, 1.810 mmol), potassium fluoride (0.210 g, 3.62 mmol), DMSO (4 ml) and DIEA (0.948 ml, 5.43 mmol). The reaction vial was capped and heated to 100° C. for 8 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed with water and then brine. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford 4-(5-chloropyridin-3-yl)-2-((2S,4R)-2-(hydroxymethyl)-4-methoxypyrrolidin-1-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C26H31ClN6O2 [M+H]+ 495. found 495.

Workup

  1. customThe reaction vial was capped
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed with water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-a6f548f42c0945a88994967bd6216af3
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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