Dobutamine hydrochloride, LY-46236, Posiject, Dobutrex, -Drug Synthesis Database

【结构式】

【药物名称】Dobutamine hydrochloride, LY-46236, Posiject, Dobutrex

【化学名称】(±)-4-[2-[3-(4-Hydroxyphenyl)-1-methylpropylamino]ethyl]-1,2-benzenediol hydrochloride

【CA登记号】49745-95-1, 34368-04-2 (free base)

【分子式】C₁₈H₂₄ClNO₃

【分子量】337.84988

【开发单位】Lilly (Originator)

【药理作用】CARDIOVASCULAR DRUGS, Heart Failure Therapy, beta1-Adrenoceptor Agonists

合成路线1 合成路线2 合成路线3

合成路线1

The reduction of 4-(p-methoxyphenyl)-3-buten-2-one (II) with hydrogen over Raney-Ni in ethyl acetate gives the corresponding butanone (III), which is then condensed with homoveratrylamine (IV) in the same solvent to give the imine (V). This product, without isolation, is reduced again with hydrogen over Pd/C to yield 3,4-dimethoxy-N-[3-(4-hydroxyphenyl)-1-methylpropyl]-beta-phenylethylamine (I), which by demethylation with HBr in refluxing acetic acid.

参考文献中间体

【1】 Castaner, J.; Thorpe, P.; Dobutamine. Drugs Fut 1977, 2, 9, 579.
【2】 Tuttle, R.R.; Mills, J. (Eli Lilly and Company); Dopamine derivatives. DE 2317710; ES 413639; FR 2182947; GB 1392674; JP 49007237 .

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)	40177	N-(3,4-dimethoxyphenethyl)-4-(4-methoxyphenyl)-2-butanamine; N-(3,4-dimethoxyphenethyl)-N-[3-(4-methoxyphenyl)-1-methylpropyl]amine		C₂₁H₂₉NO₃	详情	详情
(II)	40174	(E)-4-(4-methoxyphenyl)-3-buten-2-one	943-88-4	C₁₁H₁₂O₂	详情	详情
(III)	40175	4-(4-methoxyphenyl)-2-butanone	104-20-1	C₁₁H₁₄O₂	详情	详情
(IV)	10098	2-(3,4-Dimethoxyphenyl)-1-ethanamine; 3,4-Dimethoxyphenethylamine; 2-(3,4-Dimethoxyphenyl)ethylamine	120-20-7	C₁₀H₁₅NO₂	详情	详情
(V)	40176	N-(3,4-dimethoxyphenethyl)-N-[(E)-3-(4-methoxyphenyl)-1-methylpropylidene]amine; 2-(3,4-dimethoxyphenyl)-N-[(E)-3-(4-methoxyphenyl)-1-methylpropylidene]-1-ethanamine		C₂₁H₂₇NO₃	详情	详情

合成路线2

The Friedel-Crafts reaction of anisole (VI) with crotonyl chloride (VII) by means of AlCl3 in carbon disulfide gives p-methoxyphenyl propenyl ketone (VIII), which is then condensed with homoveratrylamine (IV) in toluene yielding 3-(3,4-dimethoxyphenylethylamino)-1-(4-methoxyphenyl)butan-1-one (IX). Finally, this ketone is reduced with hydrogen over Pd/C in ethanol to yield 3,4-dimethoxy-N-[3-(4-hydroxyphenyl)-1-methylpropyl]-beta-phenylethylamine (I), which by demethylation with HBr in refluxing acetic acid.

参考文献中间体

【1】 Castaner, J.; Thorpe, P.; Dobutamine. Drugs Fut 1977, 2, 9, 579.
【2】 Tuttle, R.R.; Mills, J. (Eli Lilly and Company); Dopamine derivatives. DE 2317710; ES 413639; FR 2182947; GB 1392674; JP 49007237 .

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)	40177	N-(3,4-dimethoxyphenethyl)-4-(4-methoxyphenyl)-2-butanamine; N-(3,4-dimethoxyphenethyl)-N-[3-(4-methoxyphenyl)-1-methylpropyl]amine		C₂₁H₂₉NO₃	详情	详情
(IV)	10098	2-(3,4-Dimethoxyphenyl)-1-ethanamine; 3,4-Dimethoxyphenethylamine; 2-(3,4-Dimethoxyphenyl)ethylamine	120-20-7	C₁₀H₁₅NO₂	详情	详情
(VI)	23767	Methoxybenzene; Methyl phenyl ether; Anisole	100-66-3	C₇H₈O	详情	详情
(VII)	40178	(E)-2-Butenoyl chloride; (E)-Crotonyl chloride	625-35-4	C₄H₅ClO	详情	详情
(VIII)	40179	(E)-1-(4-methoxyphenyl)-2-buten-1-one		C₁₁H₁₂O₂	详情	详情
(IX)	40180	3-[(3,4-dimethoxyphenethyl)amino]-1-(4-methoxyphenyl)-1-butanone		C₂₁H₂₇NO₄	详情	详情

合成路线3

The reaction of 4-(4-methoxyphenyl)-2-butylamine (X) with 3,4-dimethoxyphenylacetic acid (XI) at 200 C gives 2-(3,4-dimethoxyphenyl)-N-(4-methoxyphenyl-1-methyl-n-propyl)acetamide (XII), which is then reduced with borane in THF to yield 3,4-dimethoxy-N-[3-(4-hydroxyphenyl)-1-methylpropyl]-beta-phenylethylamine (I), which by demethylation with HBr in refluxing acetic acid.

参考文献中间体

【1】 Castaner, J.; Thorpe, P.; Dobutamine. Drugs Fut 1977, 2, 9, 579.
【2】 Tuttle, R.R.; Mills, J. (Eli Lilly and Company); Dopamine derivatives. DE 2317710; ES 413639; FR 2182947; GB 1392674; JP 49007237 .

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)	40177	N-(3,4-dimethoxyphenethyl)-4-(4-methoxyphenyl)-2-butanamine; N-(3,4-dimethoxyphenethyl)-N-[3-(4-methoxyphenyl)-1-methylpropyl]amine		C₂₁H₂₉NO₃	详情	详情
(X)	40181	4-(4-methoxyphenyl)-2-butanamine; 3-(4-methoxyphenyl)-1-methylpropylamine		C₁₁H₁₇NO	详情	详情
(XI)	40182	3-(3,4-dimethoxyphenyl)propionic acid	2107-70-2	C₁₁H₁₄O₄	详情	详情
(XII)	40183	3-(3,4-dimethoxyphenyl)-N-[3-(4-methoxyphenyl)-1-methylpropyl]propanamide		C₂₂H₂₉NO₄	详情	详情

Extended Information