Dimethyl Sulfoxide → HCID 178461252, compound

HRID 1852803Notes

Reaction equation

HRID 1852803 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.ClC1C=C([C:18]2[C:23]3[N:24]([CH2:36][C@H:37]4[CH2:42][CH2:41][C@H:40]([CH3:43])[CH2:39][CH2:38]4)[C:25](N4C[C@H](OC)C[C@H]4CO)=[N:26][C:22]=3[CH:21]=[C:20]([C:44]#[N:45])[N:19]=2)C=NC=1.C(N(CC)CC)C>ClCCl>[CH3:43][C@H:40]1[CH2:41][CH2:42][C@H:37]([CH2:36][N:24]2[C:23]3[CH:18]=[N:19][C:20]([C:44]#[N:45])=[CH:21][C:22]=3[N:26]=[CH:25]2)[CH2:38][CH2:39]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 178496639HCID 178496639, compound

Product 1

HCID 178461252HCID 178461252, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-60 °C

Procedure

A solution of oxalyl chloride (0.160 ml, 1.826 mmol) in dichloromethane (5 ml) was cooled to −78° C., and a solution of DMSO (0.259 ml, 3.65 mmol) in dichloromethane (2.5 ml) was slowly added. The reaction was warmed to −60° C. After 10 min of stirring, a solution of 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 (452 mg, 0.913 mmol) in dichloromethane (5 ml) was slowly added. The reaction was stirred for 30 min at −40° C. Then triethylamine (0.764 ml, 5.48 mmol) was added, and the reaction was warmed to room temperature and stirred overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 (30 mL). The dichloromethane layer was separated. The aqueous layer was extracted with dichloromethane (20 mL). The combined dichloromethane layers were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with EtOAc/isohexane to give 4-(5-chloropyridin-3-yl)-2-(2S,4R)-2-formyl-4-methoxypyrrolidin-1-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C26H29ClN6O2 [M+H]+ 493. found 493.

Workup

  1. stirringThe reaction was stirred for 30 min at −40° C
  2. temperaturethe reaction was warmed to room temperature
  3. stirringstirred overnight
  4. customThe reaction mixture was quenched with saturated aqueous NaHCO3 (30 mL)
  5. customThe dichloromethane layer was separated
  6. extractionThe aqueous layer was extracted with dichloromethane (20 mL)
  7. washThe combined dichloromethane layers were washed with brine (50 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography on silica gel
  12. washeluting with EtOAc/isohexane

Sources & evidence

ORD record
ord-5b98aaca62ce47b7ae3424d7c4220201
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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