Reaktion #79809

Reaktionsgleichung

maleic acid

cis-tert-butyl 4-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}-1-piperazinecarboxylate

trifluoroacetic acid dichloromethane

→

Cis-5-(4-phenoxyphenyl)-7-(4-piperazinocyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine trimaleate salt

Lösungsmittel

ethyl acetate

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvents were removed under reduced pressure
2. 2
   Sonstigethe residue was partitioned between dichloromethane (200 ml) and aqueous saturated sodium bicarbonate solution (30 ml)
3. 3
   TrocknenThe organic solution was dried over magnesium sulfate
4. 4
   Filtrationfiltered
5. 5
   Sonstigethe filtrate evaporated to a residue (1.55 g)
6. 6
   TemperaturThe mixture was cooled to ambient temperature
7. 7
   Filtrationthe solid was collected by filtration
8. 8
   Sonstigedried

Vorschrift

The cis-tert-butyl 4-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}-1-piperazinecarboxylate (1.85 g, 3.27 mmol) was treated with a 20% trifluoroacetic acid/dichloromethane solution (60 ml) and stirred for 30 minutes at ambient temperature. The solvents were removed under reduced pressure then the residue was partitioned between dichloromethane (200 ml) and aqueous saturated sodium bicarbonate solution (30 ml). The organic solution was dried over magnesium sulfate, filtered and the filtrate evaporated to a residue (1.55 g). A portion of this material (1.0 g, 2.15 mmol) was dissolved in warm ethyl acetate (220 ml) then treated with maleic acid (0.75 g, 0.44 mmol) in warm ethyl acetate (75 ml). The mixture was cooled to ambient temperature then the solid was collected by filtration and dried to give Cis-5-(4-phenoxyphenyl)-7-(4-piperazinocyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine trimaleate salt (1.15 g) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 8.5 (bs, 1H), 8.23 (s, 1H), 7.41-7.51 (m, 5H), 7.08-7.19 (m, 5H), 6.65 (bs, 2H), 6.16 (s, 6H), 4.74 (m, 1H), 1.16-3.2 (m, 17H); RP—HPLC (Hypersil CPS, 5 μm, 100 A, 250×4.6 mm; 25-100% acetonitrile-0.1 M ammonium acetate over 10 min, 1 ml/min) tr=8.63 min; MS: MH+469.

Quelle