2,5-Anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-[[[(4-methylphenyl)sulfonyl]oxy]methyl]-1-(1H-1,2,4-triazol-1-yl)-D-threo-pentitol

White Crystalline Solid

Add to 50ml single-mouth reaction bottle1-((2R, 3S)-2-(Benzyloxy)-pentan-3-yl)-4-(4-(4-(4-hydroxyphenyl)piperazin-1-yl)phenyl)- 1H-1, 2, 4-triazole-5(4H)-one (1 g, 1.947 mmol, 1 eq.), ((3S, 5R)-5-((1H-1, 2, 4-Triazol-1-yl)methyl)-5-(2, 4-difluorophenyl)tetrahydrofuran-3-yl)methyl P-toluenesulfonate (1.03g, 2.181mmol, 1.12eq.), DMSO (6 ml) was dissolved by stirring, and 50 wt% NaOH (202.5 mg, 2.531 mmol, 1.3 eq.) was added and stirred at 45 C.TLC showed complete reaction after 2 h.The reaction was dropped into water, stirred, suction filtered, and the filter cake was washed with water (50ml). Isopropanol crystallized to give 1.52g of a white solid, yield 98.7%Take 0.8mmol 5a was added to dichloromethane, was added lmmol triethylamine, 0.05mmol 4-dimethylaminopyridine. At 0 C, 1 mmol of p-toluenesulfonyl chloride was added in portions and stirred at room temperature for 1 day. The reaction was completed. The reaction mixture was poured into 1mol / L aqueous hydrochloric acid solution (20ml), methylene chloride (20ml) was added, separated and the organic phase was washed with 1mol / L hydrochloric acid (20ml) and washed with saturated Na2CO3 Dried, filtered and dried to give a yellow oil, which was purified by silica gel column chromatography to give 1 as a pure white solid with a yield of 54% and a purity of 98.0%Take 0.8mmol 5a was added to dichloromethane, was added 1mmol pyridine, 0 · 1mmol 4-dimethylaminopyridine or DMAP. 0 C added 1mmol of p-toluenesulfonyl chloride or TsCl, stirred at room temperature for 1 day, The reaction is complete. The reaction mixture was poured into 1mol / L aqueous hydrochloric acid solution (20ml), methylene chloride (20ml) was added and the mixture was separated. The organic phase was washed with 1mol / L hydrochloric acid (20ml) and then with saturated Na2CO3 Dried, filtered and spin dried to give a yellow oil. Isopropanol (5 ml) was added and the mixture was stirred for 5 min. Petroleum ether (30 ml) was added in portions and stirred for 2 hours. The mixture was filtered and washed with petroleum ether (20 ml) Solid 1, with isopropanol 30ml at 60 C recrystallization, to obtain a high purity white solid 1, a yield of 48%, a purity of 98.5%.Take 0.8mmol 5a added to dichloromethane, was added 1mmol potassium carbonate, 0.03mmol 4-dimethylaminopyridine. At 0 C, 1 mmol of p-toluenesulfonyl chloride was added in portions and stirred at room temperature for 1 day. The reaction was completed. The reaction mixture was poured into 1mol / L aqueous hydrochloric acid solution (20ml), methylene chloride (20ml) was added, separated and the organic phase was washed with 1mol / L hydrochloric acid (20ml) and washed with saturated Na2CO3 Dried, filtered and dried to give a yellow oil, which was purified by silica gel column chromatography to obtain a white solid with high purity of 1, a yield of 50% and a purity of 99.5%.To a solution of intermediate 1 (21.5 g, 66.1 mmol) in DMSO (408 mL) was added aq sodium hydroxide (28.3 mL, 3.5 M, 99.0 mmol). The mixture was stirred at RT for 30 min and was then treated portionwise with ((3S, 5R)-5-(1H-1, 2, 4-triazol-1-yl)methyl-5-(2, 4-difluorophenyl)tetrahydrofuran-3-yl)methyl4-methylbenzenesulfonate 2 (ex APIChem, Catalogue Number: AC-8330, 32.7 g, 72.7 mmol). The reaction mixture was stirred at 30C for 18 h, cooled to RT and water (600 mL) was added. The resulting mixture was extracted with EtOAc (3 x 500 mL) and the combined organic extracts were washed with sat aq NaHCC (2 x 500 mL) and with brine (500 mL) and then dried and evaporated in vacuo to afford a brown oil (approx. 41 g). Analysis of the crude, W-Boc-protected product 3 by 1 H NMR indicated that it contained approximately 10 mole % of the alkene elimination product: (R)-1-((2-(2, 4-difluorophenyl)-4-methylenetetrahydrofuran-2-yl)methyl)-1H-1, 2, 4-triazole [A], together with some unreacted starting materials. This crude product was used in the subsequent step without purification.

Posaconazole intermediate. Antifungal agent

Molecular Weight:449.5
XLogP3:3.1
Hydrogen Bond Acceptor Count:8
Rotatable Bond Count:7
Exact Mass:449.12208366
Monoisotopic Mass:449.12208366
Topological Polar Surface Area:91.7
Heavy Atom Count:31
Complexity:701
Defined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes