2-(bromomethyl)naphthalene -Drug Synthesis Database

【结构式】

【分子编号】35612

【品名】2-(bromomethyl)naphthalene

【CA登记号】939-26-4

【分子式】C₁₁H₉Br

【分子量】221.09646

【元素组成】C 59.76% H 4.1% Br 36.14%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(IV)

The previously reported chiral cyclopentanedicarboxylic acid monoester (I) was converted to the mixed anhydride (II) by treatment with ethyl chloroformate in the presence of triethylamine. Reduction of the mixed anhydride (II) with NaBH4 in cold MeOH produced the corresponding alcohol, which, under the reaction conditions, gave rise to the bicyclic lactone (III). Then, the lithium enolate generated from lactone (III) and lithium hexamethyldisilazide was alkylated with 2-(bromomethyl)naphthalene (IV) to produce the title compound.

参考文献中间体

合成目标

【1】 Horváth, E.; De Vry, J.-M.-V.; Baumgarten, J.; Schreiber, R.; Lensky, S.; Müller, T.; Stropp, U.; Voerste, A.; Müller, G.; Antonicek, H.-P.; Stolle, A.; Von dem Bruch, K. (Bayer AG); Substd. alpha,beta-anellated butyrolactones. DE 19801646; EP 1047684; WO 9936416 .

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)	27283	(1S,2R)-4-methylene-2-([[(E)-3-phenyl-2-propenyl]oxy]carbonyl)cyclopentanecarboxylic acid		C₁₇H₁₈O₄	详情	详情
(II)	51107			C₂₀H₂₂O₆	详情	详情
(III)	51108	(3aS,6aR)-5-methylenehexahydro-1H-cyclopenta[c]furan-1-one		C₈H₁₀O₂	详情	详情
(IV)	35612	2-(bromomethyl)naphthalene	939-26-4	C₁₁H₉Br	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Alkylation of N-Boc-4-(R)-hydroxyproline (I) with 2-(bromomethyl)-naphthalene (II) in the presence of NaH afforded the (naphthylmethyl) ether (III). N-Boc-norvaline (IV) was converted to the benzyl ester (V) by treatment with benzyl bromide and DBU. Subsequent acid cleavage of the Boc group of (V) yielded norvaline benzyl ester (VI). This was coupled with proline derivative (III) using HATU to give the protected dipeptide (VII).

参考文献中间体

合成目标

【1】 Rancourt, J.; Tsantrizos, Y.; Simoneau, B.; Wernic, D.; Poupart, M.-A.; Llinas-Brunet, M. (Boehringer Ingelheim (Canada) Ltd.); Hepatitis C inhibitor peptides. EP 1003775; WO 9907733 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	12912	1-(Bromomethyl)benzene; Alpha-bromotoluene	100-39-0	C₇H₇Br	详情	详情
(I)	16094	(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid;1-(tert-butoxycarbonyl)-4®-hydroxy-L-proline;(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid	16094	C₁₀H₁₇NO₅	详情	详情
(II)	35612	2-(bromomethyl)naphthalene	939-26-4	C₁₁H₉Br	详情	详情
(III)	35613	(2S,4R)-1-(tert-butoxycarbonyl)-4-(2-naphthylmethoxy)-2-pyrrolidinecarboxylic acid		C₂₁H₂₅NO₅	详情	详情
(IV)	35614	(2S)-2-[(tert-butoxycarbonyl)amino]pentanoic acid	53308-95-5	C₁₀H₁₉NO₄	详情	详情
(V)	35615	benzyl (2S)-2-[(tert-butoxycarbonyl)amino]pentanoate		C₁₇H₂₅NO₄	详情	详情
(VI)	35616	benzyl (2S)-2-aminopentanoate		C₁₂H₁₇NO₂	详情	详情
(VII)	35617	tert-butyl (2S,4R)-2-[([(1S)-1-[(benzyloxy)carbonyl]butyl]amino)carbonyl]-4-(2-naphthylmethoxy)-1-pyrrolidinecarboxylate		C₃₃H₄₀N₂O₆	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

Acylation of the 2-aminobenzophenone (I) with bromoacetyl bromide (II) provides the bromoacetamide (III). Subsequent treatment of (III) with ammonia leads to the benzodiazepinone (IV). Methylation of the lactam N with iodomethane in the presence of K2CO3 gives rise to (V). The potassium enolate of benzodiazepinone (V) is then alkylated by 2-(bromomethyl)naphthalene (VI) to furnish the naphthylmethyl derivative (VII). Finally, methyl ether cleavage using AlBr3 in ethanethiol provides the target phenolic compound

参考文献中间体

合成目标

【1】 Kim, K.; Volkman, S.K.; Ellman, J.A.; Synthesis of 3-substituted 1,4-benzodiazepin-2-ones. J Braz Chem Soc 1998, 9, 4, 375.

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)	63044			C₁₄H₁₂ClNO₂	详情	详情
(II)	14005	2-Bromoacetyl bromide; Bromoacetyl bromide	598-21-0	C₂H₂Br₂O	详情	详情
(III)	63045			C₁₆H₁₃BrClNO₃	详情	详情
(IV)	63046			C₁₆H₁₃ClN₂O₂	详情	详情
(V)	63043			C₁₇H₁₅ClN₂O₂	详情	详情
(VI)	35612	2-(bromomethyl)naphthalene	939-26-4	C₁₁H₉Br	详情	详情
(VII)	63042			C₂₈H₂₃ClN₂O₂	详情	详情

Extended Information