5,6-dihydro-3-pyridinecarbaldehyde -Drug Synthesis Database

【结构式】

【分子编号】35374

【品名】5,6-dihydro-3-pyridinecarbaldehyde

【CA登记号】

【分子式】C₆H₇NO

【分子量】109.12772

【元素组成】C 66.04% H 6.47% N 12.84% O 14.66%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

The acetylation of clarithromycin (I) with acetic anhydride gives the diacetate (II), which is acylated with CDI yielding the 12-O-(imidazolylcarbonyl compound (III). The cyclization of (III) with ethylenediamine (IV) affords the cyclic carbamate (V), which is alkylated by reductocondensation with pyridine-3-carbaldehyde (VI) and NaBH(OAc)3 to give the secondary amine (VII). The methylation of this amine with formaldehyde and NaBH(OAc)3 yields the corresponding tertiary amine (VIII), which is treated with aqueous HCl to provide the descladinosyl compound (IX). Finally, this compound is acylated with 2-(2-pyridyl)acetic acid (X) by means of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (WSC), and deacetylated with methanol to afford the target compound.

参考文献中间体

合成目标

【1】 Tanikawa, T.; Akashi, T.; Manaka, A.; Suzuki, K.; Asaka, T.; Adachi, T.; Ishii, T.; Sugiyama, H.; Kashimura, M.; Saito, H.; Morimoto, S.; Structure activity studies leading potent acyclides: 3-O-Acyl-5-O-desosaminylerythronolide 11,12-carbamates. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F2159.
【2】 Ishii, T.; Tanikawa, T.; Matsuura, A.; Sugimoto, T.; Asaka, T.; Kashimura, M. (Taisho Pharmaceutical Co., Ltd.); Erythromycin A derivs.. EP 0945459; WO 9823628 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	35358			C₃₉H₇₁NO₁₂	详情	详情
(II)	35359			C₄₃H₇₅NO₁₄	详情	详情
(III)	35360			C₄₇H₇₅N₃O₁₄	详情	详情
(IV)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情
(V)	35361			C₄₆H₇₉N₃O₁₄	详情	详情
(VI)	35374	5,6-dihydro-3-pyridinecarbaldehyde		C₆H₇NO	详情	详情
(VII)	35375			C₅₂H₈₄N₄O₁₄	详情	详情
(VIII)	35376			C₅₃H₈₆N₄O₁₄	详情	详情
(IX)	35377			C₄₃H₇₀N₄O₁₀	详情	详情
(X)	35366	2-(2-pyridinyl)acetic acid	16179-97-8	C₇H₇NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The selective hydrolysis of clarithromycin (I) with aqueous HCl, followed by acylation with acetic anhydride gives the monoacetylated descladinosyl compound (XI), which by reaction with trichloromethyl chloroformate (TCF) yields the cyclic carbonate (XII). The reaction of (XII) with 1,1,3,3-tetramethylguanidine (TMG) affords intermediate (XIII), which is selecti-ely acylated with 2-(2-pyridyl)acetic acid (X) and WSC giving the 3-O-acylated compound (XIV). The activation of (XIV) with CDI affords the 12-O-imidazolylcarbonyl derivative (XV), which is cyclized with ethylenediamine (IV) providing the carbamate (XVI). The alkylation of the primary amine of (XVI) by reductocondensation with pyridine-3-carbaldehyde (VI) and NaBH(OAc)3 gives the secondary amine (XVII).

参考文献中间体

合成目标

【1】 Tanikawa, T.; Akashi, T.; Manaka, A.; Suzuki, K.; Asaka, T.; Adachi, T.; Ishii, T.; Sugiyama, H.; Kashimura, M.; Saito, H.; Morimoto, S.; Structure activity studies leading potent acyclides: 3-O-Acyl-5-O-desosaminylerythronolide 11,12-carbamates. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F2159.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	35358			C₃₉H₇₁NO₁₂	详情	详情
(IV)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情
(VI)	35374	5,6-dihydro-3-pyridinecarbaldehyde		C₆H₇NO	详情	详情
(X)	35369	(1R,2S,4R,6R)-2-(dimethylamino)-6-[[(3R,4S,5S,6R,7R,9R,13S,14R)-14-ethyl-4,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxa-11-cyclotetradecen-6-yl]oxy]-4-methylcyclohexyl acetate		C₃₃H₅₇NO₉	详情	详情
(XI)	35367	(1R,2S,4R,6R)-2-(dimethylamino)-6-[[(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-4,12,13-trihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecanyl]oxy]-4-methylcyclohexyl acetate		C₃₃H₅₉NO₁₀	详情	详情
(XII)	35368	(1R,2R,4R,6S)-2-[[(3aR,4R,7R,8S,9S,10R,11R,13R,15R,15aR)-4-ethyl-8-hydroxy-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxododecahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecin-10-yl]oxy]-6-(dimethylamino)-4-methylcyclohexyl acetate		C₃₄H₅₇NO₁₁	详情	详情
(XIII)	35366	2-(2-pyridinyl)acetic acid	16179-97-8	C₇H₇NO₂	详情	详情
(XIV)	35370	(3R,4S,5R,6R,7R,9R,13S,14R)-6-[[(1R,2R,3S,5R)-2-(acetoxy)-3-(dimethylamino)-5-methylcyclohexyl]oxy]-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxa-11-cyclotetradecen-4-yl 2-(2-pyridinyl)acetate		C₄₀H₆₂N₂O₁₀	详情	详情
(XV)	35371	(2R,3S,7R,9R,10R,11R,12S,13R)-10-[[(1R,2R,3S,5R)-2-(acetoxy)-3-(dimethylamino)-5-methylcyclohexyl]oxy]-2-ethyl-9-methoxy-3,5,7,9,11,13-hexamethyl-6,14-dioxo-12-[[2-(2-pyridinyl)acetyl]oxy]oxa-4-cyclotetradecen-3-yl 1H-imidazole-1-carboxylate		C₄₄H₆₄N₄O₁₁	详情	详情
(XVI)	35372			C₄₃H₆₈N₄O₁₁	详情	详情
(XVII)	35378			C₄₉H₇₃N₅O₁₁	详情	详情

Extended Information