HCID 22822728, compound → HCID 22822727, compound

A solution of ε-benzyloxycarbonyl-L-lysine ethyl ester hydrochloride (2.94 g.) in water (10 ml.) is made basic with 15 ml. of saturated aqueous potassium bicarbonate and extracted with CH2Cl2. The extract is dried over MgSO4 and concentrated to dryness. The residue, ε-Benzyl oxycarbonyl-L-lysine ethyl ester, is dissolved in THF (20 ml.) and pyruvoylproline (555 mg.) and powdered No. 4A molecular sieves (1.0 g.) are added. The mixture is stirred at room temperature for 4 hours. Sodium cyanoborohydride (630 mg.) in 1 ml. of CH3OH is added over 2 hours and the mixture is stirred overnight. It is then filtered, concentrated to dryness, and the residue partitioned between water (10 ml.) and CH2Cl2 (15 ml.). The aqueous phase is absorbed on strong acid ion-exchange resin and eluted with 4% pyridine in water to yield 470 mg. of N-(1(S)-ethoxycarbonyl-5-benzyloxycarbonylaminopentyl)-D,L-alanyl-L-proline. The protecting group is removed by hydrogenation in ethanol-water 1:1 over 10 % Pd/c catalyst at 40 ps.i. The mixture is filtered and the filtrate taken to dryness. The residue in methanol is chromatographed on an LH-20 column to give the desired N-(1(S)-ethoxycarbonyl-5-aminopentyl)-D,L-alanyl-L-proline. The mass spectrum of silylated material gave a peak at 559 m/e for the trisilylated derivative and a peak at 487 m/e for the disilylated derivative. The nmr (D2O) confirmed the structure.

1. extractionof saturated aqueous potassium bicarbonate and extracted with CH2Cl2
2. dry with materialThe extract is dried over MgSO4
3. concentrationconcentrated to dryness
4. dissolutionThe residue, ε-Benzyl oxycarbonyl-L-lysine ethyl ester, is dissolved in THF (20 ml.)
5. addition4A molecular sieves (1.0 g.) are added
6. additionof CH3OH is added over 2 hours
7. stirringthe mixture is stirred overnight
8. filtrationIt is then filtered
9. concentrationconcentrated to dryness
10. customthe residue partitioned between water (10 ml.) and CH2Cl2 (15 ml.)
11. customThe aqueous phase is absorbed on strong acid ion-exchange resin
12. washeluted with 4% pyridine in water
13. customto yield 470 mg
14. customThe protecting group is removed by hydrogenation in ethanol-water 1:1 over 10 % Pd/c catalyst at 40 ps.i
15. filtrationThe mixture is filtered
16. customThe residue in methanol is chromatographed on an LH-20 column

ORD record

ord-c764031ade96499a866a5c3e722fcacd

Source dataset

uspto-grants-1984_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04472380