Hydrochloric Acid → 1-Deoxy-1-(6-((2,2-diphenylethyl)amino)-2-(((2-((((1-(2-pyridinyl)-4-piperidinyl)amino)carbonyl)amino)ethyl)amino)carbonyl)-9H-purin-9-yl)-N-ethyl-beta-D-ribofuranuronamide

To a solution of 9-{(3aR,4R,6S,6aS)-6-[(ethylamino)carbonyl]-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl}-6-[(2,2-diphenylethyl)amino]-N-{2-[({[1-(2-pyridinyl)-4-piperidinyl]amino}carbonyl)amino]ethyl}-9H-purine-2-carboxamide (Preparation 71) (20.9 g, 0.0255 moles) in absolute ethanol (200 ml) was added aqueous hydrochloric acid (76.5 ml of a 1M solution, 0.0765 moles) and the resultant solution was heated at 60–65° C. for 24 hours. The reaction mixture was allowed to cool to ambient temperature and saturated aqueous sodium bicarbonate solution (200 ml) was cautiously added. The resultant mixture was then concentrated in vacuo and the aqueous mixture was then extracted with ethyl acetate (200 ml) and then dichloromethane (200 ml). The extracts were dried over anhydrous magnesium sulphate which caused the deposition of a gum that was redissolved by the addition of dichloromethane (100 ml) and methanol (20 ml). The resultant violet solution was then concentrated in vacuo to give the crude product as a purple foam (20.86 g) that was purified by flash chromatography on silica gel (600 g) eluting with a gradient of 6% v/v methanol in dichloromethane changing to 8% v/v methanol in dichloromethane changing to 10% v/v methanol in dichloromethane changing to 15% v/v methanol in dichloromethane to give the title compound in several fractions of varying purity. The major fraction (11.4 g) was dissolved in dichloromethane (264 ml) and was filtered to remove insoluble matter. To this solution was added diethyl ether (112 ml) and the resultant cloudy mixture was stirred at ambient temperature for 1 hour. The solids were then collected by filtration and were dried in vacuo. This material was then ground using a pestle and mortar and was dried further in vacuo at 500 to give the title compound (9.9 g) as a fine colourless powder.

1. temperaturewas heated at 60–65° C. for 24 hours
2. concentrationThe resultant mixture was then concentrated in vacuo
3. extractionthe aqueous mixture was then extracted with ethyl acetate (200 ml)
4. dry with materialThe extracts were dried over anhydrous magnesium sulphate which
5. dissolutionwas redissolved by the addition of dichloromethane (100 ml) and methanol (20 ml)
6. concentrationThe resultant violet solution was then concentrated in vacuo
7. customto give the crude product as a purple foam (20.86 g) that
8. customwas purified by flash chromatography on silica gel (600 g)
9. washeluting with a gradient of 6% v/v methanol in dichloromethane changing to 8% v/v methanol in dichloromethane changing to 10% v/v methanol in dichloromethane changing to 15% v/v methanol in dichloromethane

ORD-Eintrag

ord-4737901165ba46a4813fc2f285affa0e

Quelldatensatz

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07094769B2