HCID 10374773, Verbindung → 3-(4-(3(S)-(2(S),3-Dihydroxypropanoyl)pyrrolidin-1-yl)-3-fluorophenyl)-5(S)-(isoxazol-3-ylaminomethyl)oxazolidin-2-one

3-(4-(3(S)-Aminopyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one hydrochloride salt (400 mg, 0.698 mM) in pyridine (5 ml) was treated dropwise with a solution of 2,2-dimethyl-1,3-dioxolan-4(S)-ylcarbonyl chloride (200 mg, 1.2 mM) in dichloromethane (2 ml), and the mixture stirred 3 hours at ambient temperature. The mixture was diluted with ethyl acetate (15 ml) and water (15 ml), the organic layer separated, washed with aqueous sodium bicarbonate (10 ml) and brine (10 ml), and evaporated, then azeotroped with toluene (20 ml). The residue was purified by chromatography on a 10 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 100% ethyl acetate in dichloromethane. Relevant fractions were combined and evaporated to give the desired product (435 mg ). NMR (DMSO-d6) δ: 1.30 (s, 3H); 1.37 (s, 3H); 1.89 (hextet, 1H); 2.13 (hextet, 1H); 3.20 (m, 1H); 3.24 (m overlapped by H2O, ˜1H); 3.39 (m, 1H); 3.48 (m, 1H); 3.82 (dd, 1H); 3.91 (dd, 1H); 4.12 (overlapping m, 3H); 4.33 (t overlapping m, 2H); 4.42 (dd, 2H); 4.97 (d, 1H); 5.02 (m, 1H); 5.06 (d, 1H); 6.75 (t, 1H); 6.87 (d, 1H); 7.08 (dd, 1H); 7.34 (dd, 1H); 7.94 (d, 1H); 8.89 (d, 1H). MS (ESP): 664 (MH+) for C26H29Cl3FN5O8

1. customthe organic layer separated
2. washwashed with aqueous sodium bicarbonate (10 ml) and brine (10 ml)
3. customevaporated
4. customazeotroped with toluene (20 ml)
5. customThe residue was purified by chromatography on a 10 g silica Mega Bond Elut® column
6. washeluting with
7. temperaturea gradient increasing in polarity from 0 to 100% ethyl acetate in dichloromethane
8. customevaporated

ORD-Eintrag

ord-60f8976518734c72bc0496aedeb2b5bd

Quelldatensatz

uspto-grants-2004_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06734200B1