Reaction #164774

Reaction equation

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

O-methylhydroxylamine hydrochloride

pyridine

→

N-[3-[(4aR,7aS)-2-amino-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 84.0%

Solvents

ethanol

Conditions

Workup

1. 1
   TemperatureThe reaction is cooled
2. 2
   Otherthe solvent removed in vacuo
3. 3
   OtherThe crude product is purified over silica gel with a 30 minute 0.5% to 10% gradient of 7 N ammonia in methanol dichloromethane gradient

Procedure

A mixture of 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 (320 mg, 560 μmol), O-methylhydroxylamine hydrochloride (485 mg, 5.60 mmol) and pyridine (453 μL, 5.60 mmol) in ethanol (15 mL) is heated at 65° C. in a capped vial for five hours. The reaction is cooled and the solvent removed in vacuo. The crude product is purified over silica gel with a 30 minute 0.5% to 10% gradient of 7 N ammonia in methanol dichloromethane gradient to give N-[3-[(4aR,7aS)-2-amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]phenyl]-5-fluoro-pyridine-2-carboxamide (219 mg, 84%). This material is dissolved in dichloromethane (1 mL) and methanol (0.5 mL) and 1 M hydrogen chloride in diethyl ether (0.47 mL, 470 μmol) is added. The solvent is removed in vacuo to give the title compound (228 mg, 81%). ES/MS (m/e): 468 (M+H).

Source