Reaction #164764

Reaction equation

N-[3-[(4aR,7aS)-2-benzamido-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-7a-yl]phenyl]-5-fluoro-pyridine-2-carboxamide

2,2,2-trifluoroacetic acid

5-fluoro-2-chloropyrimidine

diisopropylethylamine

5-fluoro-2-chloropyrimidine

diisopropylethylamine

5-fluoro-2-chloropyrimidine

diisopropylethylamine

→

title compound

Yield 41.0%

N-[3-[(4aR,7aS)-2-Benzamido-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]phenyl]-5-fluoro-pyridine-2-carboxamide

Yield 41.0%

Solvents

dimethyl sulfoxide

sodium carbonate

Conditions

Workup

1. 1
   Temperaturethe mixture is heated overnight at 50° C. for a third night
2. 2
   TemperatureThe reaction is cooled
3. 3
   Otherto give a slurry that
4. 4
   Filtrationis filtered
5. 5
   Otherdried in a vacuum oven at 50° C. for 4 hours

Procedure

A solution of N-[3-[(4aR,7aS)-2-benzamido-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-7a-yl]phenyl]-5-fluoro-pyridine-2-carboxamide; 2,2,2-trifluoroacetic acid (150 mg, 254 μmol), 5-fluoro-2-chloropyrimidine (68 mg, 51 μmol) and diisopropylethylamine (98 μL, 56 μmol) is heated in dimethyl sulfoxide (5 mL) overnight at 40° C. Additional 5-fluoro-2-chloropyrimidine (68 mg, 51 μmol) and diisopropylethylamine (98 μL, 56 μmol) is added and the mixture is heated overnight at 50° C. Additional 5-fluoro-2-chloropyrimidine (68 mg, 51 μmol) and diisopropylethylamine (98 μL, 56 μmol) is added and the mixture is heated overnight at 50° C. for a third night. The reaction is cooled, diluted with saturated aqueous sodium carbonate (50 mL) to give a slurry that is filtered and dried in a vacuum oven at 50° C. for 4 hours to give the title compound (60 mg, 41%). ES/MS (m/e): 449 (M+H).

Source