tert-butyl (E)-3-(3-quinolinyl)-2-propenyl carbonate -Drug Synthesis Database

【结构式】

【分子编号】46728

【品名】tert-butyl (E)-3-(3-quinolinyl)-2-propenyl carbonate

【CA登记号】

【分子式】C₁₇H₁₉NO₃

【分子量】285.3428

【元素组成】C 71.56% H 6.71% N 4.91% O 16.82%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(III)

A new synthesis of ABT-773 has been reported: The acylation of erythromycin A 9-oxime (I) with acetic anhydride, TEA and DMAP in THF gives the 2',4'',9-tri-O-acetylerythromycin A 9-oxime (II), which is first condensed with 3-(3-quinolinyl)-2-propen-1-ol tert-butyl carbonate (III) by means of Pd2(dba)3 and dppb in toluene and then treated with NaOH to yield 2',4''-di-O-acetyl-6-O-[3-(3-quinolinyl)-2-propenyl]erythromycin A 9-oxime (IV). Reaction of oxime (IV) with NaHSO3 and HOAc in water/THF affords 4''-O-acetyl-6-O-[3-(3-quinolinyl)-2-propenyl]erythromycin A (V), which is benzoylated with benzoic anhydride and TEA in isopropyl acetate/THF to provide 4''-O-acetyl-2'-O-benzoyl-6-O-[3-(3-quinolinyl)-2-propenyl]ery- thromycin A (VI). The reaction of compound (VI) with carbonyldiimidazole (CDI), sodium hexamethyldisilazide (NaHMDS) and ammonia gas in THF/DMF gives the 11-N,12-O-cyclic carbamate erythromycin A derivative (VII). The intermediate 3-(3-quinolinyl)-2-propen-1-ol tert-butyl carbonate (III) has been obtained by Grignard condensation of quinoline-3-carbaldehyde (X) with vinylmagnesium bromide (XI) in THF to give the secondary alcohol (XII), followed by esterification and simultaneous rearrangement with Boc2O in the same solvent.

参考文献中间体

合成目标

【1】 Process for preparing 6-O-substd. erythromycin derivs.. WO 0078773 .

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)	46726	(3R,4R,5R,6R,7S,9R,11S,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-14-ethyl-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13-hexamethyl-2,10-oxacyclotetradecanedione 10-oxime		C₃₇H₆₈N₂O₁₃	详情	详情
(II)	46727	(2S,3S,4R,6R)-6-([(3R,4R,5R,6R,7S,9R,11S,12R,13S,14R)-6-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-10-[(acetoxy)imino]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-2-oxooxacyclotetradecanyl]oxy)-4-methoxy-2,4-dimethyltetrahydro-2H-pyran-3-yl acetate		C₄₃H₇₄N₂O₁₆	详情	详情
(III)	46728	tert-butyl (E)-3-(3-quinolinyl)-2-propenyl carbonate		C₁₇H₁₉NO₃	详情	详情
(IV)	46729	(2S,3S,4R,6R)-6-[((3R,4R,5R,6R,7S,9R,11S,12R,13S,14R)-6-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-14-ethyl-12,13-dihydroxy-10-(hydroxyimino)-3,5,7,9,11,13-hexamethyl-2-oxo-7-[[(E)-3-(3-quinolinyl)-2-propenyl]oxy]oxacyclotetradecanyl)oxy]-4-methoxy-2,4-dimethyltetrahydro-2H-pyran-3-yl acetate		C₅₃H₈₁N₃O₁₅	详情	详情
(V)	46730	(2S,3S,4R)-6-[((3R,4R,5R,6R,7S,9R,11R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-14-ethyl-12,13-dihydroxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-7-[[(E)-3-(3-quinolinyl)-2-propenyl]oxy]oxacyclotetradecanyl)oxy]-4-methoxy-2,4-dimethyltetrahydro-2H-pyran-3-yl acetate		C₅₁H₇₈N₂O₁₄	详情	详情
(VI)	46731	(2S,3R,4S,6R)-2-[((3R,4R,5R,6R,7S,9R,11R,12R,13S,14R)-4-[[(2R,4R,5S,6S)-5-(acetoxy)-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-14-ethyl-12,13-dihydroxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-7-[[(E)-3-(3-quinolinyl)-2-propenyl]oxy]oxacyclotetradecanyl)oxy]-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl benzoate		C₅₈H₈₂N₂O₁₅	详情	详情
(VII)	46732	(2S,3R,4S,6R)-2-[((3aS,4R,7R,8R,9R,10R,11S,13R,15R,15aR)-8-[[(2R,4R,5S,6S)-5-(acetoxy)-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxo-11-[[(E)-3-(3-quinolinyl)-2-propenyl]oxy]tetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl)oxy]-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl benzoate		C₅₉H₈₁N₃O₁₅	详情	详情
(VIII)	35362	3-quinolinecarbaldehyde	13669-42-6	C₁₀H₇NO	详情	详情
(IX)	46733	chloro(vinyl)magnesium	3536-96-7	C₂H₃ClMg	详情	详情
(X)	46734	1-(3-quinolinyl)-2-propen-1-ol		C₁₂H₁₁NO	详情	详情

Extended Information