methyl 4-amino-2-(1-naphthyl)benzoate -Drug Synthesis Database

【结构式】

【分子编号】27705

【品名】methyl 4-amino-2-(1-naphthyl)benzoate

【CA登记号】

【分子式】C₁₈H₁₅NO₂

【分子量】277.32264

【元素组成】C 77.96% H 5.45% N 5.05% O 11.54%

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：(III)

4-Hydroxybenzaldehyde (I) was alkylated with 2,2,3,3-tetrafluoropropyl tosylate (A) to give ether (II). Subsequent Horner-Emmons condensation of (II) with triethyl phosphonocrotonate (III) provided dienoate (IV), that was further reduced to alcohol (V) by means of DIBAL. Oxidation of (V) with activated MnO2 then gave aldehyde (VI).

参考文献中间体

合成目标

【1】 Tajima, Y.; Oida, S.; Konosu, T.; et al.; Synthesis and antifungal activities of R-102557 and related dioxane-triazole derivatives. Chem Pharm Bull 2000, 48, 5, 694.
【2】 Oida, S.; Tanaka, T.; Tajima, Y.; Konosu, T.; Somada, A.; Miyaoka, T.; Yasuda, H. (Sankyo Co., Ltd.); Triazole antifungal agent. EP 0841327; JP 1996333350; US 5977152; WO 9631491 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	41331	2,2,3,3-tetrafluoropropyl 4-methylbenzenesulfonate		C₁₀H₁₀F₄O₃S	详情	详情
(I)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(II)	15481	4-(2,2,3,3-tetrafluoropropoxy)benzaldehyde		C₁₀H₈F₄O₂	详情	详情
(III)	27705	methyl 4-amino-2-(1-naphthyl)benzoate		C₁₈H₁₅NO₂	详情	详情
(IV)	41332	ethyl (2E,4E)-5-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-pentadienoate		C₁₆H₁₆F₄O₃	详情	详情
(V)	41333	(2E,4E)-5-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-pentadien-1-ol		C₁₄H₁₄F₄O₂	详情	详情
(VI)	41334	(2E,4E)-5-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-pentadienal		C₁₄H₁₂F₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Suzuki coupling of methyl 2-bromo-4-nitrobenzoate (I) with 1-naphthylboronic acid (II) provided naphthyl benzoate ester (III). The nitro group of (III) was then reduced by hydrogenation over Pd/C yielding aniline (IV). Diazotization of (IV), followed by reaction with KI gave aryl iodide (V), and subsequent halogen displacement by KCN in the presence of palladium catalyst afforded nitrile (VI). After basic hydrolysis of the methyl ester of (VI), the resulting carboxylic acid (VII) was coupled to L-leucine methyl ester (VIII) using EDC and HOBt to yield amide (IX). Reduction of the nitrile group of (IX) with NaBH4 and CoCl2 gave the corresponding amine, which was isolated as the tert-butyl carbamate (X) upon treatment with Boc2O.

参考文献中间体

合成目标

【1】 Vasudevan, A.; et al.; Potent, highly selective, and non-thiol inhibitors of protein geranylgeranyltransferase-I. J Med Chem 1999, 42, 8, 1333.

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)	27702	methyl 2-bromo-4-nitrobenzoate		C₈H₆BrNO₄	详情	详情
(II)	27703	1-naphthylboronic acid	13922-41-3	C₁₀H₉BO₂	详情	详情
(III)	27704	methyl 2-(1-naphthyl)-4-nitrobenzoate		C₁₈H₁₃NO₄	详情	详情
(IV)	27705	methyl 4-amino-2-(1-naphthyl)benzoate		C₁₈H₁₅NO₂	详情	详情
(V)	27706	methyl 4-iodo-2-(1-naphthyl)benzoate		C₁₈H₁₃IO₂	详情	详情
(VI)	27707	methyl 4-cyano-2-(1-naphthyl)benzoate		C₁₉H₁₃NO₂	详情	详情
(VII)	27708	4-cyano-2-(1-naphthyl)benzoic acid		C₁₈H₁₁NO₂	详情	详情
(VIII)	27709	methyl (2S)-2-amino-4-methylpentanoate		C₇H₁₅NO₂	详情	详情
(IX)	27710	methyl (2S)-2-[[4-cyano-2-(1-naphthyl)benzoyl]amino]-4-methylpentanoate		C₂₅H₂₄N₂O₃	详情	详情
(X)	27711	methyl (2S)-2-[[4-[[(tert-butoxycarbonyl)amino]methyl]-2-(1-naphthyl)benzoyl]amino]-4-methylpentanoate		C₃₀H₃₆N₂O₅	详情	详情

Extended Information