Reaktion #10433

Reaktionsgleichung

3-amino-1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-7-thiosulfonic acid

Compound 24c

3-amino-1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-7-thiosulfonic acid

((R)-(S)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester

triethylamine

→

title compound

Ausbeute 58.7%

{(S)-1-[(R)-1-(3-Amino-1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-7-yl)pyrrolidin-3-yl]ethyl}-carbamic acid tert-butyl ester

Ausbeute 58.7%

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAIT50° C. for 1 hour
2. 2
   SonstigeThe solvent is removed in vacuo
3. 3
   Sonstigethe residue is partitioned between ethyl acetate (50 mL) and water (25 mL)
4. 4
   WaschenThe organic layer is washed with water
5. 5
   Trocknendried (MgSO4)
6. 6
   Filtrationfiltered
7. 7
   Sonstigeevaporated in vacuo
8. 8
   Sonstigeto give 0.28 g
9. 9
   WaschenChromatography on flash grade silica gel (230–400 mesh) column (2×12 cm) eluting with dichloromethane/ethanol (95:5)

Vorschrift

A solution of 0.12 g (0.38 mmol) of 3-amino-1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-7-thiosulfonic acid (Compound 24c) in 10 mL of acetonitrile is treated with 0.24 g (1.14 mmol) of ((R)-(S)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester (J. Het. Chem., 1992; 29:1481), 0.25 g (2.5 mmol) of triethylamine and stirred at room temperature for 18 hours then 50° C. for 1 hour. The solvent is removed in vacuo and the residue is partitioned between ethyl acetate (50 mL) and water (25 mL). The organic layer is washed with water, dried (MgSO4), filtered and evaporated in vacuo to give 0.28 g. Chromatography on flash grade silica gel (230–400 mesh) column (2×12 cm) eluting with dichloromethane/ethanol (95:5) provided 0.1 g of the title compound, mp 175–177° C.

Quelle