Dimethyl Sulfoxide → HCID 68584397, compound

HRID 17602Notes

Reaction equation

HRID 17602 reaction equation
CS(C)=O.[CH3:5][NH:6][C@H:7]1[CH2:11][CH2:10][NH:9][CH2:8]1.[C:12]([C:14]1[C:19]2[N:20]=[C:21]([C:23]([N:25]([CH2:27][CH2:28][O:29][CH3:30])[CH3:26])=[O:24])[O:22][C:18]=2[C:17](F)=[C:16]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:15]=1[CH3:38])#[N:13].C(N(CC)CC)C>[Cl-].[Na+].O.C(Cl)(Cl)Cl>[C:12]([C:14]1[C:19]2[N:20]=[C:21]([C:23]([N:25]([CH2:27][CH2:28][O:29][CH3:30])[CH3:26])=[O:24])[O:22][C:18]=2[C:17]([N:9]2[CH2:10][CH2:11][C@H:7]([NH:6][CH3:5])[CH2:8]2)=[C:16]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:15]=1[CH3:38])#[N:13]

Participants

7

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 8471TriethylamineHCID 10261057(3S)-(-)-3-(Methylamino)pyrrolidineHCID 68584983HCID 68584983, compound

Product 1

HCID 68584397HCID 68584397, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Under nitrogen atmosphere, a dimethyl sulfoxide (1 ml) solution of (3S)-3-(methylamino)pyrrolidine (109 μl, 1.03 mmol) was added at 140 to 150° C. to a dimethyl sulfoxide (8 ml) solution of 4-cyano-7-fluoro-N-(2-methoxyethyl)-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide (I-122) (314 mg, 855 μmol) and triethylamine (155 μl, 1.11 mmol), followed by stirring at the same temperature for 50 minutes. After cooling, saturated brine was added to the reaction liquid, and the mixture liquid was extracted with ethyl acetate. Next, the combined organic layer was washed with saturated brine, then dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by middle-pressure liquid chromatography (eluent, dichloromethane:methanol=10:1, v/v) to obtain a rough product of the entitled compound. The rough product of the entitled compound was dissolved in chloroform, washed with an aqueous saturated sodium hydrogencarbonate solution, then the aqueous layer was extracted with chloroform. The combined organic layer was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the entitled compound (117 mg, 31%) as an amorphous substance.

Workup

  1. temperatureAfter cooling
  2. extractionthe mixture liquid was extracted with ethyl acetate
  3. washNext, the combined organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resulting residue was purified by middle-pressure liquid chromatography (eluent, dichloromethane
  8. custommethanol=10:1, v/v) to obtain a rough product of the entitled compound
  9. washwashed with an aqueous saturated sodium hydrogencarbonate solution
  10. extractionthe aqueous layer was extracted with chloroform
  11. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-efd1391c653b483e9820a7b16ee53988
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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