6-(methoxycarbonyl)-2'-methyl[1,1'-biphenyl]-3-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】38999

【品名】6-(methoxycarbonyl)-2'-methyl[1,1'-biphenyl]-3-carboxylic acid

【CA登记号】

【分子式】C₁₆H₁₄O₄

【分子量】270.28476

【元素组成】C 71.1% H 5.22% O 23.68%

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：(IV)

Palladium-catalyzed coupling of dimethyl iodoterephthalate (I) with 2-methylphenylboronic acid (II) furnished the biphenyl derivative (III). Regioselective ester hydrolysis of (III) under controlled conditions provided the mono acid (IV), which was further reduced to alcohol (V) using borane in THF. After hydrolysis of the remaining ester function of (V), the resulting carboxylic acid (VI) was coupled to L-methionine methyl ester (VII), yielding amide (VIII). Swern oxidation of the alcohol function of (VIII) gave aldehyde (IX). This was then subjected to a reductive amination with amine (X) in the presence of NaBH(OAc)3 to afford the secondary amine (XI). The methyl ester group of (XI) was finally hydrolyzed with LiOH.

参考文献中间体

合成目标

【1】 Tasker, A.S.; Wasicak, J.; Henry, K.J. Jr.; et al.; PDB-093. Drug Data Rep 1995, 17, 2, 138.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIIII)	43757	methyl (2S)-2-([[5-(hydroxymethyl)-2'-methyl[1,1'-biphenyl]-2-yl]carbonyl]amino)-4-(methylsulfanyl)butanoate		C₂₁H₂₅NO₄S	详情	详情
(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)	43756	5-(hydroxymethyl)-2'-methyl[1,1'-biphenyl]-2-carboxylic acid		C₁₅H₁₄O₃	详情	详情
(VII)	17950	D-Methionine methyl ester; methyl (2S)-2-amino-4-(methylsulfanyl)butanoate hydrochloride	21691-49-6	C₆H₁₃NO₂S	详情	详情
(IX)	43758	methyl (2S)-2-[[(5-formyl-2'-methyl[1,1'-biphenyl]-2-yl)carbonyl]amino]-4-(methylsulfanyl)butanoate		C₂₁H₂₃NO₄S	详情	详情
(X)	43759	(2S)-1-cyclohexyl-3-(ethylsulfanyl)-2-propanamine; (1S)-2-cyclohexyl-1-[(ethylsulfanyl)methyl]ethylamine		C₁₁H₂₃NS	详情	详情
(XI)	43760	methyl (2S)-2-[([5-[([(1S)-2-cyclohexyl-1-[(ethylsulfanyl)methyl]ethyl]amino)methyl]-2'-methyl[1,1'-biphenyl]-2-yl]carbonyl)amino]-4-(methylsulfanyl)butanoate		C₃₂H₄₆N₂O₃S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

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

合成目标

【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

Extended Information