ABT-839, A-228839, A-228839.25(sulfate), -Drug Synthesis Database

【结构式】

【药物名称】ABT-839, A-228839, A-228839.25(sulfate)

【化学名称】N-[5-[N-Butyl-N-(2-cyclohexylethyl)aminomethyl]-2'-methylbiphenyl-2-ylcarbonyl]-L-methionine

【CA登记号】216234-25-2 (Li salt)

【分子式】C₃₂H₄₆N₂O₃S

【分子量】538.79902

【开发单位】University of Pittsburgh (Originator), Abbott (Codevelopment)

【药理作用】ONCOLYTIC DRUGS, Farnesyl Transferase Inhibitors, Inhibitors of Signal Transduction Pathways

合成路线1 合成路线2

合成路线1

Palladium-catalyzed coupling of dimethyl iodoterephthalate (I) with 2-methylphenylboronic acid (II) afforded biphenyl (III). Hydrolysis of (III) with LiOH yielded mono acid (IV), which was reduced to alcohol (V) using borane in cold THF. Subsequent reaction of (V) with PBr3 furnished the intermediate bromide (VI).

参考文献中间体

【1】 Donner, B.G.; Janowick, D.A.; Larsen, J.J.; Rosenberg, S.H.; Hamilton, A.D.; Barr, K.J.; Sorensen, B.K.; Augeri, D.J.; Kalvin, D.M.; O'Connor, S.J.; Fakhoury, S.A.; Swenson, R.E.; Liu, G.; Sebti, S.M.; Shen, W. (University of Pittsburgh); Inhibitors of protein isoprenyl transferases. EP 0986384; WO 9850029; WO 9850030; WO 9850031 .

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)	38996	dimethyl 2-iodoterephthalate		C₁₀H₉IO₄	详情	详情
(II)	38997	2-methylphenylboronic acid	16419-60-6	C₇H₉BO₂	详情	详情
(III)	38998	dimethyl 2'-methyl[1,1'-biphenyl]-2,5-dicarboxylate		C₁₇H₁₆O₄	详情	详情
(IV)	38999	6-(methoxycarbonyl)-2'-methyl[1,1'-biphenyl]-3-carboxylic acid		C₁₆H₁₄O₄	详情	详情
(V)	39000	methyl 5-(hydroxymethyl)-2'-methyl[1,1'-biphenyl]-2-carboxylate		C₁₆H₁₆O₃	详情	详情
(VI)	39001	methyl 5-(bromomethyl)-2'-methyl[1,1'-biphenyl]-2-carboxylate		C₁₆H₁₅BrO₂	详情	详情

合成路线2

Cyclohexylacetic acid (VII) was converted to acid chloride and then condensed with n-butyl amine to give amide (VIII). Reduction of (VIII) with LiAlH4 afforded secondary amine (IX), which was alkylated with bromide (VI) yielding amino ester (X). After basic hydrolysis of the ester group of (X), the resultant carboxylic acid (XI) was coupled with L-methionine methyl ester (XII) to produce amide (XIII). The methyl ester group of (XIII) was finally hydrolyzed by treatment with LiOH.

参考文献中间体

【1】 Donner, B.G.; Janowick, D.A.; Larsen, J.J.; Rosenberg, S.H.; Hamilton, A.D.; Barr, K.J.; Sorensen, B.K.; Augeri, D.J.; Kalvin, D.M.; O'Connor, S.J.; Fakhoury, S.A.; Swenson, R.E.; Liu, G.; Sebti, S.M.; Shen, W. (University of Pittsburgh); Inhibitors of protein isoprenyl transferases. EP 0986384; WO 9850029; WO 9850030; WO 9850031 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	39001	methyl 5-(bromomethyl)-2'-methyl[1,1'-biphenyl]-2-carboxylate		C₁₆H₁₅BrO₂	详情	详情
(VII)	39002	2-cyclohexylacetic acid	5292-21-7	C₈H₁₄O₂	详情	详情
(VIII)	39003	N-butyl-2-cyclohexylacetamide		C₁₂H₂₃NO	详情	详情
(IX)	39004	N-(2-cyclohexylethyl)-1-butanamine; N-butyl-N-(2-cyclohexylethyl)amine		C₁₂H₂₅N	详情	详情
(X)	39005	methyl 5-[[butyl(2-cyclohexylethyl)amino]methyl]-2'-methyl[1,1'-biphenyl]-2-carboxylate		C₂₈H₃₉NO₂	详情	详情
(XI)	39006	5-[[butyl(2-cyclohexylethyl)amino]methyl]-2'-methyl[1,1'-biphenyl]-2-carboxylic acid		C₂₇H₃₇NO₂	详情	详情
(XII)	17950	D-Methionine methyl ester; methyl (2S)-2-amino-4-(methylsulfanyl)butanoate hydrochloride	21691-49-6	C₆H₁₃NO₂S	详情	详情
(XIII)	39007	methyl (2S)-2-[[(5-[[butyl(2-cyclohexylethyl)amino]methyl]-2'-methyl[1,1'-biphenyl]-2-yl)carbonyl]amino]-4-(methylsulfanyl)butanoate		C₃₃H₄₈N₂O₃S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)