Lithium Hydroxide → (R)-2-{5-Chloro-2-[3-(2-methylpiperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophene-4-carboxylic acid methylamide

Temperatur

90 °C

A stirred mixture of 2-(2,5-dichloropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid methylamide (0.30 g, 0.89 mmol), (R)-4-(3-aminopropyl)-3-methylpiperazine-1-carboxylic acid tert-butyl ester (0.57 g, 2.2 mmol) and diisopropylethylamine (0.29 g, 2.2 mmol) in 1,4-dioxane (5 mL) is heated at 90° C. under a nitrogen atmosphere for 14 hours. After concentration and subsequent chromatography on silica gel, eluting with 2 M NH3/MeOH in dichloromethane 0-8%, the intermediate is obtained as a solid. The solid is suspended in dichloromethane (3 mL), followed by the successive addition of triethylsilane (0.50 mL) and TFA (3 mL). The resultant yellow solution is stirred for 7 hours. After concentration a wet solid is obtained. The solid is treated with 2 N LiOH, with sonication, until pH reaches 12. The mixture is filtered, the solid is dried before it is subject to chromatography on silica gel, eluting with 2 M NH3/MeOH in dichloromethane 0-20%, to give the title compound as a yellow solid (190 mg, 46% yield). ES+(m/z) 459 (35Cl) and 461 (37Cl) [M+H].

1. concentrationAfter concentration and subsequent chromatography on silica gel
2. washeluting with 2 M NH3/MeOH in dichloromethane 0-8%
3. customthe intermediate is obtained as a solid
4. concentrationAfter concentration a wet solid
5. customis obtained
6. filtrationThe mixture is filtered
7. customthe solid is dried before it
8. washeluting with 2 M NH3/MeOH in dichloromethane 0-20%

ORD-Eintrag

ord-262dbbb1cc374d6db764a17da58a714d

Quelldatensatz

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07547691B2