Dimethylformamide → 6-Chloro famciclovir

Reaktionsgleichung

[C:1]([O:4][CH2:5][CH:6]([CH2:10][CH2:11]CCBr)[C:7]([O-:9])=O)(=[O:3])[CH3:2].[NH2:15][C:16]1[N:24]=[C:23]2[C:19]([NH:20][CH:21]=[N:22]2)=[C:18]([Cl:25])[N:17]=1.[C:26](=[O:29])([O-])[O-].[K+].[K+].[CH3:32]N(C)C=O>>[C:26]([O:9][CH2:7][CH:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])[CH2:10][CH2:11][N:22]1[CH:21]=[N:20][C:19]2[C:23]1=[N:24][C:16]([NH2:15])=[N:17][C:18]=2[Cl:25])(=[O:29])[CH3:32]

Komponenten

Edukt 4

HCID 6228Dimethylformamide

HCID 11430Potassium Carbonate

HCID 53603492-Amino-6-chloropurine

HCID 867453192-Acetoxymethyl-4-bromobut-1-yl-acetate

Produkt 1

HCID 101551646-Chloro famciclovirAusbeute 80 %

Versuchsvorschrift

A mixture of 2-acetoxymethyl-4-bromobut-1-yl-acetate (13.0 g, 48.7 mmol), 2-amino-6-chloro-purine (8.25 g, 48.7 mmol) and anhydrous potassium carbonate (10 g, 72.5 mmol) was stirred in dry dimethylformamide (100 ml) for 18 hours at room temperature. The reaction mixture was then filtered, the filtrate evaporated, and the residue purified by column chromatography on silica gel (500 g). Elution with 3% methanol in chloroform afforded 9-(4-acetoxy-3-acetoxymethyl-but-1-yl)-2-amino-6-chloropurine as a white solid (13.8 g, 80%) mp 135°-137°. λmax (H2 0) 222 (ε28,500), 245 (ε4,800) 307 (ε7,700) nm; νmax (KBr)3485, 3310, 3200, 1750, 1730, 1625, 1560, 1525, 1475, 1245 cm-1. δH [(CD3)2SO] (270 MHz) 1.85-2.05 (3 H, m, CHCH2CH2), 2.01 (6 H, s, 2×OCOCH3), 4.03 (4 H, d, 2×CH2OCOCH3), 4.16 (2 H, t, CH2N), 6.88 (2 H, br s, D2O exchangeable, NH2), 8.17 (1 H, s, 8-H). Found C, 47.27; H, 4.94; N, 19.56%. C14H18N5O4Cl requires C, 47.26; H, 5.10; N 19.68%.