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

HRID 17397Notes

Reaction equation

HRID 17397 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]([CH3:28])[CH3:27])=[O:25])[O:23][C:19]=2[C:18](F)=[C:17]([C:30]2[N:31]=[C:32]([CH3:35])[S:33][CH:34]=2)[C:16]=1[CH3:36])#[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]([CH3:28])[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:30]2[N:31]=[C:32]([CH3:35])[S:33][CH:34]=2)[C:16]=1[CH3:36])#[N:14]

Participants

6

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 8471TriethylamineHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 685848584-cyano-7-fluoro-N,N,5-trimethyl-6-(2-methyl-1,3-thiazol-4-yl)-1,3-benzoxazole-2-carboxamide

Product 1

HCID 685862634-cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-N,N,5-trimethyl-6-(2-methyl-1,3-thiazol-4-yl)-1,3-benzoxazole-2-carboxamide

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

Under nitrogen atmosphere, a dimethyl sulfoxide (2 ml) solution of (3S)-3-(dimethylamino)pyrrolidine (442 μl, 3.48 mmol) was added at 140 to 150° C. to a dimethyl sulfoxide (56 ml) solution of 4-cyano-7-fluoro-N,N,5-trimethyl-6-(2-methyl-1,3-thiazol-4-yl)-1,3-benzoxazole-2-carboxamide (I-129) (1.00 g, 2.90 mmol) and triethylamine (525 μl, 3.77 mmol), followed by stirring at the same temperature for 10 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, 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 (10:1, v/v) gave a crude product of the entitled compound as a solid, and the solid was suspended and washed in diethyl ether to obtain the entitled compound (670 mg, 53%) as a yellow solid. The fraction containing impurities and the filtrate in suspension washing were recovered and purified in the same manner to obtain 145 mg of the entitled compound, 815 mg (64%) of the entitled compound was obtained in total.

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-665828390e54412c8b4aacdeaf1b8aeb
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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