Dimethyl Sulfoxide → 4-Cyano-N,N,5-trimethyl-7-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-6-phenyl-1,3-benzoxazole-2-carboxamide

HRID 17375Notes

Reaction equation

HRID 17375 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]([CH3:27])[CH3:26])=[O:24])[O:22][C:18]=2[C:17](F)=[C:16]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:15]=1[CH3:35])#[N:13].[CH2:36](N(CC)CC)C>[Cl-].[Na+].O>[C:12]([C:14]1[C:19]2[N:20]=[C:21]([C:23]([N:25]([CH3:27])[CH3:26])=[O:24])[O:22][C:18]=2[C:17]([N:9]2[CH2:10][CH2:11][C@@H:7]([N:6]([CH3:36])[CH3:5])[CH2:8]2)=[C:16]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:15]=1[CH3:35])#[N:13]

Participants

6

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 8471TriethylamineHCID 10261056(3R)-(+)-3-(Methylamino)pyrrolidineHCID 510423354-Cyano-7-fluoro-N,N,5-trimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide

Product 1

HCID 685853894-Cyano-N,N,5-trimethyl-7-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-6-phenyl-1,3-benzoxazole-2-carboxamideYield 23%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

Under nitrogen atmosphere, a dimethyl sulfoxide (2 ml) solution of (3R)-3-methylaminopyrrolidine (85 μl, 660 μmol) was added at 150° C. to a dimethyl sulfoxide (11 ml) solution of 4-cyano-7-fluoro-N,N,5-trimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide (I-114) (180 mg, 557 μmol) and triethylamine (101 μl, 724 μmol), followed by stirring at the same temperature for 30 minutes. After cooling, saturated brine was added to the reaction liquid, and the reaction liquid was extracted with chloroform. 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 preparative silica gel column chromatography. The eluate with chloroform/methanol (10:1, v/v) gave the entitled compound (53 mg, 23%) as a white amorphous substance.

Workup

  1. temperatureAfter cooling
  2. customthe reaction liquid
  3. extractionwas extracted with chloroform
  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-8a6762ba6ab24b5cabc718b66a9cf14a
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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