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

HRID 17386Notes

Reaction equation

HRID 17386 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][CH2:29][O:30][CH3:31])[CH3:27])=[O:25])[O:23][C:19]=2[C:18](F)=[C:17]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:16]=1[CH3:39])#[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][CH2:29][O:30][CH3:31])[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:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:16]=1[CH3:39])#[N:14]

Participants

6

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 8471TriethylamineHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 68584983HCID 68584983, compound

Product 1

HCID 685840324-cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-N-(2-methoxyethyl)-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamideYield 53%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

Under nitrogen atmosphere, a dimethyl sulfoxide (2 ml) solution of (3S)-3-(dimethylamino)pyrrolidine (70 μl, 552 μmol) was added at 150° C. to a dimethyl sulfoxide (7 ml) solution of 4-cyano-7-fluoro-N-(2-methoxyethyl)-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide (I-122) (169 mg, 460 μmol) and triethylamine (83 μl, 598 μmol), followed by stirring at the same temperature for 2 hours. 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, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography, and the eluate with dichloromethane/methanol (20:1, v/v) gave the entitled compound (112 mg, 53%) 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 reduced pressure

Sources & evidence

ORD record
ord-55918d8f8dcc41e5813a9bda5311737f
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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