合成路线:The condensation of 2-chloro-4-(piperidin-1-ylmethyl)pyridine (V) with 4-(tetrahydropyranyloxy)-2(Z)-buten-1-ol (VI) by means of NaH in THF gives 4-(piperidin-1-ylmethyl)-2-[4-(tetrahydropyranyloxy)-2(Z)-butenyloxy)pyridine (VII),which is deprotected with 4-methylbenzenesulfonic acid in methanol,yielding the free butenol (VIII).The acylation of (VIII) with methanesulfonyl chloride in toluene affords the corresponding mesylate (IX),which is finally condensed with 2-(2-furylmethylsulfonyl)acetamide (X) (obtained from the corresponding 4-nitrophenyl ester (XI) with ammonia) by means of potassium tert-butoxide in toluene.
参考文献标题:Methods of producing amino butene derivs
文献作者:Iwata,H.; Matsumoto,H.; Matsumoto,M.; Sekine,Y.; Nishimura,M.; Hosoda,A.(UCB Japan)
参考来源:EP 0582304; JP 1994192195
合成路线:1) The reaction of 2-bromo-4-(piperidin-1-ylmethyl)pyridine (I) with 4-amino-2(Z)-buten-1-ol (II) by means of NaH in THF gives 4-[4-(piperidin-1-ylmethyl)pyridin-2-yloxy]-2(Z)-buten-1-amine (III),which is then condensed with 2-(2-furylmethylsulfinyl)acetic acid (IV) by means of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDCD) in dichloromethane.
合成路线:The condensation of 2-chloro-4-(piperidin-1-ylmethyl)pyridine (V) with 4-(tetrahydropyranyloxy)-2(Z)-buten-1-ol (VI) by means of NaH in THF gives 4-(piperidin-1-ylmethyl)-2-[4-(tetrahydropyranyloxy)-2(Z)-butenyloxy)pyridine (VII),which is deprotected with 4-methylbenzenesulfonic acid in methanol,yielding the free butenol (VIII).The acylation of (VIII) with methanesulfonyl chloride in toluene affords the corresponding mesylate (IX),which is finally condensed with 2-(2-furylmethylsulfonyl)acetamide (X) (obtained from the corresponding 4-nitrophenyl ester (XI) with ammonia) by means of potassium tert-butoxide in toluene.
参考文献标题:Lafutidine
文献作者:Graul,A.; Prous,J.; Castar,J.
参考来源:Drugs Fut 1994,19(9),835
合成路线:A new synthesis of lafutidine has been described: The condensation of 2-bromopyridine-4-carbaldehyde ethylene ketal (I) with 4-(tetrahydropyranyloxy)-2(Z)-buten-1-ol (II) by means of NaOH,K2CO3 and tetrabutylammonium bisulfate in refluxing toluene gives the corresponding substitution product (III),which by treatment with pyridinium p-toluenesulfonate (PPTS) in hot ethanol yields the 2(Z)-butenol (IV).The reaction of (IV) with SOCl2 and then with potassium phthalimide (V) affords the substituted phthalimide (VI),which by treatment with hydrazine hydrate in refluxing methanol gives the 2(Z)-butenamine (VII).The condensation of (VII) with 2-(2-furylmethylsulfinyl)acetic acid 4-nitrophenyl ester (VIII) in THF yields the expected amide (IX),which is treated with p-toluenesulfonic acid in refluxing acetone/water to eliminate the ethylene ketal protecting group yilding the aldehyde (X).Finally,this compound is reductocondensed with piperidine (XI) by means of NaBH4 in ethanol.
参考文献标题:A novel histamine 2(H2) receptor antagonist with gastroprotective activity.II.Synthesis and pharmacological evaluation of 2-furfuryl-thio and 2-furfurylsulfinyl acetamide derivatives with heteroaromatic rings
文献作者:Hirakawa,N.; Matsumoto,H.; Hosoda,A.; Sekine,A.; Yamaura,T.; Sekine,Y.
参考来源:Chem Pharm Bull 1998,46(4),616
产品链接: CAS No. 118288-08-7››