Hh-Ag 1.2, -Drug Synthesis Database

【结构式】

【药物名称】Hh-Ag 1.2

【化学名称】3-Chloro-N-(4'-cyano-6-methoxybiphenyl-3-ylmethyl)-N-[4-(methylamino)cyclohexyl]-1-benzothiophene-2-carboxamide

【CA登记号】364590-54-5, 364590-91-0 (hydrochloride)

【分子式】C₃₁H₃₀ClN₃O₂S

【分子量】544.12065

【开发单位】Curis (Originator), Elan (Codevelopment)

【药理作用】Antiparkinsonian Drugs, Extrapyramidal Disorders, Treatment of, NEUROLOGIC DRUGS, Smo Receptor Agonists

合成路线1 合成路线2

合成路线1

1,4-Diaminocyclohexane (I) is converted into the mono-carbamate (II) employing di-tert-butyl dicarbonate in cold THF. Subsequent reduction of carbamate (II) by means of LiAlH4 leads to the N-methyl amine (III). After blocking the primary amino group of (III) as the corresponding benzaldimine (IV), treatment with di-tert-butyl dicarbonate gives rise to the mono-protected diamine (V). (1,2)

参考文献中间体

【1】 Baxter, A.D.; Boyd, E.A.; Price, S.; Guicherit, O.M.; Porter, J.; Rubin, L.E. (Curis, Inc.); Small organic molecule regulators of cell proliferation. US 6613798; US 6683108; WO 0174344 .
【2】 Baxter, A.D.; Boyd, E.A.; Price, S.; Guicherit, O.M.; Porter, J.; Rubin, L.; Stibbard, J.H.A. (Curis, Inc.); Small organic molecule regulators of cell proliferation. US 2002198236; WO 0327234 .

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)	43407	4-aminocyclohexylamine; 1,4-cyclohexanediamine	3114-70-3	C₆H₁₄N₂	详情	详情
(II)	43408	tert-butyl 4-aminocyclohexylcarbamate		C₁₁H₂₂N₂O₂	详情	详情
(III)	63695	N~1~-methyl-1,4-cyclohexanediamine		C₇H₁₆N₂	详情	详情
(IV)	63696	N~1~-methyl-N~4~-(phenylmethylidene)-1,4-cyclohexanediamine		C₁₄H₂₀N₂	详情	详情
(V)	63697	1,1-dimethylethyl 4-aminocyclohexyl(methyl)carbamate		C₁₂H₂₄N₂O₂	详情	详情

合成路线2

Suzuki coupling between 2-methoxy-5-formylphenylboronic acid (VI) and 4-bromobenzonitrile (VII) affords the biphenyl aldehyde (VIII). This is then reductively condensed with amine (V) in the presence of NaBH(OAc)3 to furnish (IX). Acylation of amine (IX) with 3-chlorobenzo[b]thiophene-2-carbonyl chloride (X) leads to amide (XI). The N-Boc protecting group of (XI) is finally removed with ethanolic HCl to provide the title compound. (1,2)

参考文献中间体

【1】 Baxter, A.D.; Boyd, E.A.; Price, S.; Guicherit, O.M.; Porter, J.; Rubin, L.E. (Curis, Inc.); Small organic molecule regulators of cell proliferation. US 6613798; US 6683108; WO 0174344 .
【2】 Baxter, A.D.; Boyd, E.A.; Price, S.; Guicherit, O.M.; Porter, J.; Rubin, L.; Stibbard, J.H.A. (Curis, Inc.); Small organic molecule regulators of cell proliferation. US 2002198236; WO 0327234 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	63697	1,1-dimethylethyl 4-aminocyclohexyl(methyl)carbamate		C₁₂H₂₄N₂O₂	详情	详情
(VI)	63698	5-formyl-2-(methyloxy)phenylboronic acid		C₈H₉BO₄	详情	详情
(VII)	45833	4-Bromobenzonitrile	623-00-7	C₇H₄BrN	详情	详情
(VIII)	63699	3'-formyl-6'-(methyloxy)[1,1'-biphenyl]-4-carbonitrile		C₁₅H₁₁NO₂	详情	详情
(IX)	63700			C₂₇H₃₅N₃O₃	详情	详情
(X)	63701	3-chloro-1-benzothiophene-2-carbonyl chloride		C₉H₄Cl₂OS	详情	详情
(XI)	63702	1,1-dimethylethyl 4-([(3-chloro-1-benzothiophen-2-yl)carbonyl]{[4'-cyano-6-(methyloxy)[1,1'-biphenyl]-3-yl]methyl}amino)cyclohexyl(methyl)carbamate		C₃₆H₃₈ClN₃O₄S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)