Reaktion #10430

Reaktionsgleichung

5-amino-8,9-difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diazaphenalene-4,6-dione

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

triethylamine

→

title compound

Ausbeute 73.7%

{(S)-1-[(R)-1-(5-Amino-8-fluoro-3-methyl-4,6-dioxo-2,3,5,6-tetrahydro-4H-1-oxa-3a,5-diazaphenalen-9-yl)pyrrolidin-3-yl]ethyl}carbamic acid tert-butyl ester

Ausbeute 73.7%

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturat reflux for 18 hours
2. 2
   SonstigeThe solvent is removed in vacuo
3. 3
   Sonstigethe residue is partitioned between ethyl acetate/water
4. 4
   WaschenThe organic layer is washed with water
5. 5
   Trocknendried (MgSO4)
6. 6
   Einengenconcentrated in vacuo
7. 7
   SonstigeThe residue is chromatographed over flash grade silica gel (230–400 mesh)
8. 8
   Wascheneluting with dichloromethane/ethanol (95:5)

Vorschrift

A solution of 0.11 g (0.41 mmol) of 5-amino-8,9-difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diazaphenalene-4,6-dione (Example 24h), 0.26 g (1.3 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 10 mL of acetonitrile is heated at reflux for 18 hours. The solvent is removed in vacuo and the residue is partitioned between ethyl acetate/water. The organic layer is washed with water, dried (MgSO4) and concentrated in vacuo. The residue is chromatographed over flash grade silica gel (230–400 mesh) eluting with dichloromethane/ethanol (95:5) to give 0.14 g of the title compound. 1H NMR (400 MHz, CDCl3): 7.43 (d, 1H), 5.24 (bs, 2H), 4.82 (m, 1H), 4.56 (m, 1H), 4.33 (d, 1H), 3.99 (m, 1H), 3.86 (m, 1H), 3.73 (m, 1H), 3.59 (m, 2H), 2.18 (m, 1H), 3.01 (m, 1H), 1.67 (m, 1H), 1.44 (s, 9H), 1.40 (m, 3H), 1.25 (m, 1H), 1.20 (d, 3H).

Quelle