2-(1-Benzothiophen-4-yl)acetyl chloride -Drug Synthesis Database

【结构式】

【分子编号】11050

【品名】2-(1-Benzothiophen-4-yl)acetyl chloride

【CA登记号】

【分子式】C₁₀H₇ClOS

【分子量】210.68368

【元素组成】C 57.01% H 3.35% Cl 16.83% O 7.59% S 15.22%

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：(VII)

A new synthesis of [14C]-PD-117302 has been described: The Reformatsky condensation of 4,5,6,7-tetrahydrobenzo[b]thiophen-4-one (II) with methyl [1-14C]-bromoacetate (I) by means of Zn in reflux toluene gives a mixture of methyl [1-14C]-2-(4,5,6,7-tetrahydrobenzothiophen-4-ylidene)acete (III) and methyl [1-14C]-2-(6,7-dihdyrobenzothiophen-4-yl)acetate (IV) which, without separation, are treated with Pd/C and S in refluxing N-methylpyrrolidone to afford methyl [1-14C]-2-(benzothiophen-4-yl)acetate (V). The hydrolysis of (V) with methanolic KOH yields the corresponding acid (VI), which is treated with refluxing SOCl2 to give the acyl chloride (VII). Finally, this compound is condensed with trans-1-[2-(methylamino)cyclohexyl]pyrrolidine (VIII) in dichloromethane ethyl ether.

参考文献中间体

合成目标

【1】 Huang, C.C.; Hicks, J.L.; Butler, D.E.; Hays, S.J.; Synthesis of carbon-14 labeled PD 117,302 and PD 126,212, potential new analgesic agents. J Label Compd Radiopharm 1990, 28, 1, 15.

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)	11044	methyl 2-bromo-2-methylpropanoate; methyl 2-bromo-2-methylpropionate	23426-63-3	C₅H₉BrO₂	详情	详情
(I)	63069	methyl 2-bromo-2-methylpropanoate		C₅H₉BrO₂	详情	详情
(II)	11045	6,7-Dihydro-1-benzothiophen-4(5H)-one; 4-Keto-4,5,6,7-tetrahydrothianaphthene; Tetrahydrobenzo(b)thiophene-4-one	13414-95-4	C₈H₈OS	详情	详情
(III)	11046	methyl 2-[6,7-dihydro-1-benzothiophen-4(5H)-ylidene]acetate		C₁₁H₁₂O₂S	详情	详情
(III)	63070	methyl 2-[6,7-dihydro-1-benzothiophen-4(5H)-ylidene]acetate		C₁₁H₁₂O₂S	详情	详情
(IV)	11047	methyl 2-(6,7-dihydro-1-benzothiophen-4-yl)acetate		C₁₁H₁₂O₂S	详情	详情
(IV)	63071	methyl 2-(6,7-dihydro-1-benzothiophen-4-yl)acetate		C₁₁H₁₂O₂S	详情	详情
(V)	11048	methyl 2-(1-benzothiophen-4-yl)acetate		C₁₁H₁₀O₂S	详情	详情
(V)	63072	methyl 2-(1-benzothiophen-4-yl)acetate		C₁₁H₁₀O₂S	详情	详情
(VI)	11049	2-(1-Benzothiophen-4-yl)acetic acid		C₁₀H₈O₂S	详情	详情
(VI)	63073	2-(1-benzothiophen-4-yl)acetic acid		C₁₀H₈O₂S	详情	详情
(VII)	11050	2-(1-Benzothiophen-4-yl)acetyl chloride		C₁₀H₇ClOS	详情	详情
(VII)	63074	2-(1-benzothiophen-4-yl)acetyl chloride		C₁₀H₇ClOS	详情	详情
(VIII)	11051	(1S,2S)-N-Methyl-2-(1-pyrrolidinyl)cyclohexanamine; N-Methyl-N-[(1S,2S)-2-(1-pyrrolidinyl)cyclohexyl]amine		C₁₁H₂₂N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Ring opening of cyclohexene oxide (I) with aqueous methylamine gave trans 2-(methylamino)cyclohexanol (II), which was further cyclized to the aziridine (III) upon treatment with chlorosulfonic acid and then with NaOH. Subsequent condensation of (III) with pyrrolidine (IV) yielded the racemic trans diamine (V). Resolution was achieved by fractional crystallization of the 2,3-di-p-toluoyl-D-tartaric acid salt in MeOH. The required (-)-(R,R) enantiomer was finally coupled with 4-benzothiopheneacetyl chloride (VI) to provide the corresponding amide.

参考文献中间体

合成目标

【1】 MacLeod, B.A.; Walker, M.J.A.; Wall, R.A. (University of British Columbia); Aminocyclohexylamides for antiarrhythmic and anaesthetic uses. EP 0632806; JP 1995505151; US 5506257; WO 9319056 .
【2】 Bain, A.I. (Nortran Pharmaceuticals Inc.); Mixtures of enantiomers of aminocyclohexylamides to produce simultaneous analgesia with local anaesthesia or antiarrhythmia. WO 9916431 .
【3】 Halfpenny, P.R.; Schofield, D.; Hughes, J.; Rees, D.C.; Jarvis, T.C.; Hill, R.G.; Horwell, D.C.; Clark, C.R.; Highly selective kappa opioid analgesics. Synthesis and structure-activity relationships of novel N-[(2-aminocyclohexyl)aryl]acetamide and N-[(2-aminocyclohexyl)aryloxy]acetamide derivatives. J Med Chem 1988, 31, 4, 831.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11021	Methanamine; Methylamine	74-89-5	CH₅N	详情	详情
(+)-(V)	11051	(1S,2S)-N-Methyl-2-(1-pyrrolidinyl)cyclohexanamine; N-Methyl-N-[(1S,2S)-2-(1-pyrrolidinyl)cyclohexyl]amine		C₁₁H₂₂N₂	详情	详情
(-)-(V)	31357	N-methyl-N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]amine; (1R,2R)-N-methyl-2-(1-pyrrolidinyl)cyclohexanamine		C₁₁H₂₂N₂	详情	详情
(I)	17986	7-oxabicyclo[4.1.0]heptane; cyclohexene oxide	286-20-4	C₆H₁₀O	详情	详情
(II)	31355	(1R,2R)-2-(methylamino)cyclohexanol		C₇H₁₅NO	详情	详情
(III)	31356	7-methyl-7-azabicyclo[4.1.0]heptane		C₇H₁₃N	详情	详情
(IV)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(VI)	11050	2-(1-Benzothiophen-4-yl)acetyl chloride		C₁₀H₇ClOS	详情	详情

Extended Information