Hydrochloric Acid → 2-[2-[(4aR,7aR)-2-Amino-7a-isothiazol-5-yl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-6-yl]-5-fluoro-6-methyl-pyrimidin-4-yl]propan-2-ol hydrochloride

Temperatur

70 °C

N-[(4aR,7aR)-6-[5-Fluoro-4-(1-hydroxy-1-methyl-ethyl)-6-methyl-pyrimidin-2-yl]-7a-isothiazol-5-yl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (33 mg, 0.064 mmol) is dissolved in ethanol (2 mL). To this solution is added pyridine (0.052 mL, 0.6 mmol) and O-methylhydroxylamine hydrochloride (55 mg, 0.6 mmol). The reaction is warmed to 70° C. for 4 hours. The reaction is cooled to room temperature and stirred overnight (˜16 hrs). The mixture is concentrated to give the crude product which is purified via silica gel chromatography using a 0-10% (7 N NH3 in MeOH)/DCM to give the pure freebase. The freebase is dissolved in DCM (2 mL) and treated with 4 M HCl in dioxane (0.3 mL, 1.2 mmol). The mixture is concentrated to give the title compound as a white solid (18 mg, 0.04 mmol). ES/MS (m/z): 409 (M+H). [α]D20=−6.0° (C=1.0, MeOH).

1. temperatureThe reaction is cooled to room temperature
2. concentrationThe mixture is concentrated
3. customto give the crude product which
4. customis purified via silica gel chromatography
5. customto give the pure freebase
6. concentrationThe mixture is concentrated

ORD-Eintrag

ord-cd89b06d82c6459b8be55e0293dd9e8e

Quelldatensatz

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08629270B2