Dimethyl Sulfoxide → HCID 59261048, compound

HRID 643578Notes

Reaction equation

HRID 643578 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH:11]([C@:14]1([C:26]([N:28]2[CH2:33][C:32]3[CH:34]=[C:35]([C:38]([F:41])([F:40])[F:39])[CH:36]=[CH:37][C:31]=3[O:30][CH2:29]2)=[O:27])[CH2:18][CH2:17][C@@H:16]([N:19]2[CH2:24][CH2:23][CH:22]([OH:25])[CH2:21][CH2:20]2)[CH2:15]1)([CH3:13])[CH3:12].C(N(CC)CC)C.C(=O)=O.CC(C)=O>C(Cl)Cl>[CH:11]([C@:14]1([C:26]([N:28]2[CH2:33][C:32]3[CH:34]=[C:35]([C:38]([F:39])([F:40])[F:41])[CH:36]=[CH:37][C:31]=3[O:30][CH2:29]2)=[O:27])[CH2:18][CH2:17][C@@H:16]([N:19]2[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]2)[CH2:15]1)([CH3:13])[CH3:12]

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 11178180HCID 11178180, compoundHCID 18522661Acetone cardice

Product 1

HCID 59261048HCID 59261048, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of oxalyl chloride (35.0 μL, 0.402 mmol) in 15 mL of DCM was cooled to −78° C. DMSO (57.0 L, 0.805 mmol) was added drop-wise to the stirring solution. After 5 min 1-((1R,3S)-3-isopropyl-3-{[6-(trifluoromethyl)-2H-1,3-benzoxazin-3(4H)-yl]carbonyl}cyclopentyl)piperidin-4-ol (EXAMPLE 13, TABLE 1, 88 mg) in 5 mL of DCM was added drop-wise over 3 min to the reaction. After stirring for an additional 25 min at −78° C., triethylamine (224.0 μL, 1.609 mmol) in 5 mL of DCM was added drop-wise over 1 min. The reaction mixture was stirred at −78° C. for 10 min before the dry ice/acetone bath was removed. The reaction was allowed to warm to rt and stirred for 1.5 h. The reaction mixture was then diluted with DCM (50 mL) and washed with 1N HCl solution (1×75 mL), sodium bicarbonate solution (1×75 mL), and brine (1×75 mL). The aqueous layers were combined and extracted with dichloromethane (5×100 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification by preparatory TLC (silica gel, 0.4% ammonium hydroxide, 3.6% MeOH, 96% DCM) afforded 1-((1R,3S)-3-isopropyl-3-{[6-(trifluoromethyl)-2H-1,3-benzoxazin-3(4H)-yl]carbonyl}cyclopentyl)piperidin-4-one. ESI-MS calculated for C23H29F3N2O3: 438.48, found 457 (hydrate+H).

Workup

  1. customto the reaction
  2. customwas removed
  3. temperatureto warm to rt
  4. stirringstirred for 1.5 h
  5. additionThe reaction mixture was then diluted with DCM (50 mL)
  6. washwashed with 1N HCl solution (1×75 mL), sodium bicarbonate solution (1×75 mL), and brine (1×75 mL)
  7. extractionextracted with dichloromethane (5×100 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification by preparatory TLC (silica gel, 0.4% ammonium hydroxide, 3.6% MeOH, 96% DCM)

Sources & evidence

ORD record
ord-2423612cd702446cb8c0fbcd144a4258
Source dataset
uspto-grants-2010_04
Patent number
US07700591B2

Reaction notes

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