Atenolol, ICI-66082, Blokium, Tenormin, -Drug Synthesis Database

【结构式】

【药物名称】Atenolol, ICI-66082, Blokium, Tenormin

【化学名称】2-[4-[2-Hydroxy-3-(isopropylamino)propoxy]phenyl]acetamide

【CA登记号】29122-68-7

【分子式】C₁₄H₂₂N₂O₃

【分子量】266.34304

【开发单位】Pfizer (Proprietary), AstraZeneca (Originator), Almirall Prodesfarma (Licensee)

【药理作用】Acute Myocardial Infarction, Treatment of, Angina pectoris, Treatment of, Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, Heart Failure Therapy, Hypertension, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, beta1-Adrenoceptor Antagonists

合成路线1 合成路线2

合成路线1

This compound has been obtained by two related ways: 1) The reaction of phenol (I) with formaldehyde gives 4-(hydroxymethyl)phenol (II), which is treated with NaCN in hot DMF to yield 2-(4-hydroxyphenyl)acetonitrile (III). The hydrolysis of (III) in refluxing ethanol/water, catalyzed by a Pt catalyst affords the corresponding acetamide (IV), which is condensed with an excess of hot epichlorohydrin (V) by means of piperidine gives 2-[4-(2-oxiranylmethoxy)phenyl]acetamide (VI). Finally, the oxirane ring of (VI) is opened with isopropylamine in methanol. 2)The condensation of acetonitrile (III) with epichlorohydrin (V) as before gives the 2-[4-(2-oxiranylmethoxy)phenyl]acetonitrile (VIII), which is treated with isopropylamine (VII) in methanol yielding 2-[4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl]acetonitrile (IX). Finally, this compound is hydrolyzed with refluxing ethanol/water catalyzed by a Pt catalyst as before to afford the target acetamide.

参考文献中间体

【1】 Akisanya, J.; et al.; A synthesis of atenolol using a nitrile hydration catalyst. Org Process Res Dev 1998, 2, 4, 274.

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)	23540	Phenol	108-95-2	C₆H₆O	详情	详情
(II)	29474	4-(hydroxymethyl)phenol; 4-hydroxyphenylmethanol 4-hydroxybenzenemethanol; 4-Hydroxybenzyl alcohol	623-05-2	C₇H₈O₂	详情	详情
(III)	32753	2-(4-hydroxyphenyl)acetonitrile; 4-Hydroxybenzyl cyanide	14191-95-8	C₈H₇NO	详情	详情
(IV)	32754	p-Hydroxyphenylacetamide; 2-(4-hydroxyphenyl)acetamide; 4-Hydroxybenzeneacetamide; 4-Hydroxyphenylacetamide	17194-82-0	C₈H₉NO₂	详情	详情
(V)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(VI)	32755	2-[4-(2-oxiranylmethoxy)phenyl]acetamide		C₁₁H₁₃NO₃	详情	详情
(VII)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情
(VIII)	32756	2-[4-(2-oxiranylmethoxy)phenyl]acetonitrile		C₁₁H₁₁NO₂	详情	详情
(IX)	32757	2-[4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl]acetonitrile		C₁₄H₂₀N₂O₂	详情	详情

合成路线2

Prepared in two steps by condensation of p-hydroxyphenylacetamide (I) and epichlorhydrine (II) with piperidine as catalyst, giving 1-(p-carbamoylmethylphenoxy)-2,3-epoxypropane (III), m.p. 158-60 C, followed by reaction of the epoxy ring with isopropylamine (IV).

参考文献中间体

【1】 Barret, A.; et al.; Alkanolaminderivate. CH 547257; CH 553747; DE 2007751; ES 376788; FR 2034561 .
【2】 Castaner, J.; Atenolol. Drugs Fut 1976, 1, 1, 7.

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)	32754	p-Hydroxyphenylacetamide; 2-(4-hydroxyphenyl)acetamide; 4-Hydroxybenzeneacetamide; 4-Hydroxyphenylacetamide	17194-82-0	C₈H₉NO₂	详情	详情
(II)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(III)	32755	2-[4-(2-oxiranylmethoxy)phenyl]acetamide		C₁₁H₁₃NO₃	详情	详情
(IV)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情

Extended Information