Dimethyl Sulfoxide → HCID 178494118, compound

HRID 1068845Notes

Reaction equation

HRID 1068845 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([O:19][CH3:20])[N:14]=3)=[C:11]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[N:10]=[CH:9]2)[CH2:4][CH2:3]1.C(N(CC)CC)C.O.[CH3:36][S:37]([CH3:39])=O>C(OCC)(=O)C>[F:27][C:24]1[CH:23]=[CH:22][C:21]([C:11]2[N:10]=[CH:9][N:8]([C@H:5]3[CH2:6][CH2:7][C@H:2]([O:1][CH2:36][S:37][CH3:39])[CH2:3][CH2:4]3)[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([O:19][CH3:20])[N:14]=2)=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 962WaterHCID 8471TriethylamineHCID 178494117HCID 178494117, compound

Product 1

HCID 178494118HCID 178494118, compoundYield 5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

The product of example 11 (7.76 g, 21 mmol) was dissolved with warming in DMSO (105 mL) while stirring under argon. Cooling to room temperature and addition of triethylamine (29 mL, 208 mmol) resulted in two phases. The mixture was cooled with stirring to 18° C. in a water bath. The sulfur trioxide pyridine complex (13.4 g, 84 mmol) in DMSO (42 mL) was added dropwise over 15 min. The mild exotherm was controlled by adding ice to the water bath. The maximum internal temperature was 20° C. After the addition was complete, the mixture was stirred for 15 min., diluted with ethyl acetate (800 mL) and extracted four times with water (500 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and evaporated on a rotary evaporator to give 7.9 g of a crude product which NMR indicated contained −5% of the title compound. The remainder of the crude material was mostly 5-[4-(2-methoxy)pyrimidinyl]-4-(4-fluorophenyl)-1-(4-oxocyclohexyl)imidazole. Careful chromatography on silica gel (700 g) eluted with 0.5-3% methanol in methylene chloride gave the title product as a white solid (0.368 g, 4%). MS(ES+) [M+H]+, 429.

Workup

  1. customresulted in two phases
  2. temperatureThe mixture was cooled
  3. stirringwith stirring to 18° C. in a water bath
  4. customwas 20° C
  5. additionAfter the addition
  6. stirringthe mixture was stirred for 15 min.
  7. extractionextracted four times with water (500 mL)
  8. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customevaporated on a rotary evaporator
  11. customto give 7.9 g of a crude product which NMR

Sources & evidence

ORD record
ord-2d63a83f71404068aea2707bca666de1
Source dataset
uspto-grants-2001_06
Patent number
US06251914B1

Reaction notes

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