3,6-二硫杂-1,8-辛二醇

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To (S)-[1-(2-{4-[3-(4-chloro-phenyl)-prop-2-ynyloxy]-3-methoxy-phenyl}ethylcarbamoyl)-2-methyl-propyl]-carbamic acid-tert.-butyl ester (18 g) in tetrahyrofuran (180 ml), Lindlar-catalyst (5%-Pd on CaSO4; 7.2 g), 3,6-dithia-1,8-octandiol (45 mg) and 2,2′-(ethylenedithio)-diethanol (45 mg) are added. The resulting mixture is shaken under a hydrogen atmosphere at room temperature and at normal pressure for 5 hours. It is then filtered and evaporated. The residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 1:2) and recrystallised (ethyl acetate/hexane). Z-(S)-[1-(2-{4-[3-(4-Chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethylcarbamoyl)-2-methyl-propyl]-carbamic acid-tert.-butyl ester is obtained, m.p. 82-84° C. It is then filtered evaporated The residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 1:2) recrystallised (ethyl acetate/hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl 4-(4-hydroxybut-2-yn-1-yl)piperidine-1-carboxylate from step 2 of this example (10.6 g, 41.8 mmol) was dissolved in 200 mL MeOH and 3,6-Dithia-1,8-octanediol (191 mg, 1.05 mmol) was added, followed by Lindlar's catalyst (5% w/w, 4.45 g, 2.1 mmol). The reaction vessel was degassed and back filled with hydrogen 3 times and further stirred under a hydrogen balloon at room temperature for 1 hour. The reaction was filtered through Celite and concentrated under vacuum to afford the crude product as colorless oil which was used directly in the next step. The reaction vessel was degassed back filled with hydrogen 3 times The reaction was filtered through Celite concentrated under vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In an ice bath, 25 g of dithioglycol was stirred and thereto, was added dropwise 1.1 equivalent of a methanol solution of sodium methoxide. Further, 44 g of ethylene chlorohydrin was added dropwise thereto. After the conclusion of the dropwise addition, the reaction mixture was allowed to stand for 10 hours at a room temperature. Then, sodium chloride deposited was removed by filtration, and the resulting filtrate was concentrated. The thus obtained white crystals were recrystallized from acetone. Melting Point 65° C., Yield 25 g. After the conclusion of the dropwise addition Then, sodium chloride deposited was removed by filtration the resulting filtrate was concentrated The thus obtained white crystals were recrystallized from acetone

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-(3,3-dimethylbut-1-yn-1-yl)-4-methylisoxazole-3-carboxamide (Example 7, Step 3)) (30 mg, 0.075 mmol) in EtOAc (3 mL) was treated with 2,2′-(ethane-1,2-diylbis(sulfanediyl))diethanol (13.72 mg, 0.075 mmol) and Pd-5% Barium sulphate (16.02 mg, 7.53 μmol). The mixture was degassed, thoroughly refilling with nitrogen and the mixture was stirred under an atmosphere of hydrogen at room temperature overnight. Further Pd-5% Barium sulphate (16.02 mg, 7.53 μmol) was added and the reaction mixture was stirred at room temperature under an atmosphere of hydrogen for 16 hours. The resulting mixture was filtered through Celite® eluting with EtOAc and the solvent was removed under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 0-100% EtOAc in iso-hexane afforded the title compound; The mixture was degassed the reaction mixture was stirred at room temperature under an atmosphere of hydrogen for 16 hours The resulting mixture was filtered through Celite® eluting with EtOAc the solvent was removed under reduced pressure The crude material was adsorbed onto silica and purification by chromatography eluting with 0-100% EtOAc in iso-hexane