Dimethyl Sulfoxide → HCID 178461252, compound

HRID 1852802Notes

Reaction equation

HRID 1852802 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](C3C=NC=C(Cl)C=3)=[N:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=2[N:3]=1.[F-].[K+].CS(C)=O.CCN(C(C)C)C(C)C>C(OCC)(=O)C>[CH3:27][C@H:24]1[CH2:25][CH2:26][C@H:21]([CH2:20][N:19]2[C:5]3[CH:6]=[N:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=3[N:3]=[CH:2]2)[CH2:22][CH2:23]1

Participants

6

Reactant 4

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

Product 1

HCID 178461252HCID 178461252, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

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-8efa332bff8b4fbdbd0cda42665285d6
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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