Dimethyl Sulfoxide → 4-cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-N-ethyl-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide

HRID 17575Notes

Reaction equation

HRID 17575 reaction equation
CS(C)=O.[CH3:5][N:6]([CH3:12])[C@H:7]1[CH2:11][CH2:10][NH:9][CH2:8]1.[C:13]([C:15]1[C:20]2[N:21]=[C:22]([C:24]([N:26]([CH2:28][CH3:29])[CH3:27])=[O:25])[O:23][C:19]=2[C:18](F)=[C:17]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:16]=1[CH3:37])#[N:14].C(N(CC)CC)C>[Cl-].[Na+].O>[C:13]([C:15]1[C:20]2[N:21]=[C:22]([C:24]([N:26]([CH2:28][CH3:29])[CH3:27])=[O:25])[O:23][C:19]=2[C:18]([N:9]2[CH2:10][CH2:11][C@H:7]([N:6]([CH3:12])[CH3:5])[CH2:8]2)=[C:17]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:16]=1[CH3:37])#[N:14]

Participants

6

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 8471TriethylamineHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 685857964-cyano-N-ethyl-7-fluoro-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide

Product 1

HCID 685847994-cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-N-ethyl-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamideYield 52.2%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

Under nitrogen atmosphere, a dimethyl sulfoxide (1 ml) solution of (3S)-3-(dimethylamino)pyrrolidine (80 μl, 633 μmol) was added at 140 to 150° C. to a dimethyl sulfoxide (10 ml) solution of 4-cyano-N-ethyl-7-fluoro-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide (I-285) (178 mg, 528 μmol) and triethylamine (96 μl, 686 μmol), followed by stirring at the same temperature for 165 minutes. After cooling, saturated brine was added to the reaction liquid, and the reaction 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 the reduced pressure. The resulting residue was purified by preparative TLC (eluent, dichloromethane:methanol=10:1, v/v) to obtain the entitled compound (119 mg, 52%) as an amorphous substance.

Workup

  1. temperatureAfter cooling
  2. customthe reaction liquid
  3. extractionwas extracted with ethyl acetate
  4. washNext, the combined organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under the reduced pressure
  8. customThe resulting residue was purified by preparative TLC (eluent, dichloromethane

Sources & evidence

ORD record
ord-1a3a264f435c4e92af7ebaecfc79a6a4
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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