1-(bromomethyl)-4-(tert-butyl)benzene -Drug Synthesis Database

【结构式】

【分子编号】20588

【品名】1-(bromomethyl)-4-(tert-butyl)benzene

【CA登记号】18880-00-7

【分子式】C₁₁H₁₅Br

【分子量】227.1441

【元素组成】C 58.17% H 6.66% Br 35.18%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(II)

By condensation of N-methyl-1-naphthylmethylamine (I) with 4-(tert-butyl)benzyl bromide (II) by means of Na2CO3 in DMF, followed by acidification with HCl in ethanol.

参考文献中间体

合成目标

【1】 Arai, K.; Arita, M.; Sedino, T.; Komoto, N.; Hirose, S. (Mitsui Toatsu Chem.; Inc.); Benzylamine derivatives, process for production thereof, and use thereof. EP 0221781 .
【2】 Prous, J.; Castaner, J.; KP-363. Drugs Fut 1989, 14, 4, 315.

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)	10108	N-Methyl(1-naphthyl)methanamine; N-Methyl-N-(1-naphthylmethyl)amine; 1-Methyl-1-naphthalenemethylamine	65473-13-4	C₁₂H₁₃N	详情	详情
(II)	20588	1-(bromomethyl)-4-(tert-butyl)benzene	18880-00-7	C₁₁H₁₅Br	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Grignard reagent (II), prepared from 4-tert-butylbenzyl bromide (I) and magnesium in Et2O, was condensed with estrone (III) to provide the 17-(tert-butylbenzyl)estradiol (IV). Subsequent reaction of (IV) with sulfamoyl chloride in the presence of 2,6-di-tert-butyl-4-methylpyridine (DBMP) yielded the title sulfamate ester.

参考文献中间体

合成目标

【1】 Labrie, F.; Boivin, R.P.; Luu-The, V.; Ciobanu, L.C.; Poirier, D.; Potent inhibition of steroid sulfatase activity by 3-O-sulfamate 17alpha-Benzyl(or 4'-tert-butylbenzyl)estra-1,3,5(10)-trienes: Combination of two substituents at positions C3 and c17alpha of estradiol. J Med Chem 1999, 42, 12, 2280.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	40598	amidosulfonoyl chloride	7778-42-9	H₂ClNO₂S	详情	详情
(I)	20588	1-(bromomethyl)-4-(tert-butyl)benzene	18880-00-7	C₁₁H₁₅Br	详情	详情
(II)	34441	bromo[4-(tert-butyl)benzyl]magnesium		C₁₁H₁₅BrMg	详情	详情
(III)	20468	(8R,9S,13S,14S)-3-hydroxy-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one	53-16-7	C₁₈H₂₂O₂	详情	详情
(IV)	34442	(8R,9S,13S,14S,17R)-17-[4-(tert-butyl)benzyl]-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,17-diol		C₂₉H₃₈O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

N-Methyl-L-leucine (IV) was converted to tert-butyl ester (V) by treatment with isobutylene and H2SO4. Formation of the N,N-dialkyl derivative (VIII) was achieved by either alkylation of (V) with p-tert-butylbenzyl bromide (VI) or by reductive condensation of (V) with p-tert-butylbenzaldehyde (VII) and NaBH(OAc)3. Deprotection of the tert-butyl ester of (VIII) with trifluoroacetic acid gave amino acid (IX), which was activated as the mixed anhydride (X) upon treatment with isobutyl chloroformate and a polymer-supported morpholine base. Coupling of (X) with tyrosine amide (III) then afforded the title dipeptide amide. Unreacted starting materials were captured by the addition of polymer-supported polyamine and isocyanate resins.

参考文献中间体

合成目标

【1】 Ryder, T.R.; et al.; Multiple parallel synthesis of N,N-dialkyldipeptidylamines as N-type calcium channel blockers. Bioorg Med Chem Lett 1999, 9, 13, 1813.
【2】 Szoke, B.G.; Rafferty, M.F.; Silva, D.F.; Song, Y.; Malone, T.C.; Hu, L.-Y.; Urge, L.; Nadasdi, L.; Ryder, T.R. (Neurex Corp.; Pfizer Inc.); Substd. peptidylamine calcium channel blockers. WO 9854123 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	30798	(2S)-2-amino-3-[4-(benzyloxy)phenyl]-N-(tert-butyl)propanamide		C₂₀H₂₆N₂O₂	详情	详情
(IV)	34642	(2S)-4-methyl-2-(methylamino)pentanoic acid		C₇H₁₅NO₂	详情	详情
(V)	26296	tert-butyl (2S)-4-methyl-2-(methylamino)pentanoate		C₁₁H₂₃NO₂	详情	详情
(VI)	20588	1-(bromomethyl)-4-(tert-butyl)benzene	18880-00-7	C₁₁H₁₅Br	详情	详情
(VII)	16638	4-(tert-butyl)benzaldehyde; 4-tert-Butyl-benzaldehyde	939-97-9	C₁₁H₁₄O	详情	详情
(VIII)	34643	tert-butyl (2S)-2-[[4-(tert-butyl)benzyl](methyl)amino]-4-methylpentanoate		C₂₂H₃₇NO₂	详情	详情
(IX)	34644	(2S)-2-[[4-(tert-butyl)benzyl](methyl)amino]-4-methylpentanoic acid		C₁₈H₂₉NO₂	详情	详情
(X)	34645			C₂₃H₃₇NO₄	详情	详情

合成路线4

该中间体在本合成路线中的序号：(III)

Maleimide (I) was brominated in the presence of benzoyl peroxide to give 3,4-dibromomaleimide (II). Alkylation of (II) with 4-(tert-butyl)benzyl bromide (III) in the presence of potassium carbonate afforded the N-(tert-butylbenzyl) derivative (IV). Coupling of the dibromomaleimide (IV) with the indolylmagnesium iodide resulting from 5-fluoroindole (V) and MeMgI furnished the bis-indolyl maleimide (VI). Oxidative cyclization of (VI) using dicyanodichlorobenzoquinone yielded the target indolopyrrolocarbazole system (VIII). Glycosylation of (VIII) with the protected fluoro glucose derivative (VIII) under Mitsunobu conditions afforded adduct (IX). The O-benzyl protecting groups were then removed by transfer hydrogenation with cyclohexene and Pd(OH)2 to give (X). The tert-butylbenzyl group was finally removed by basic hydrolysis followed by recyclization with fused ammonium acetate.

参考文献中间体

合成目标

【1】 Saulnier, M.G.; Balasubramanian, N.; Frennesson, D.B.; St. Laurent, D.R.; Langley, D.R. (Bristol-Myers Squibb Co.); Cytotoxic amino sugar and related sugar derivs. of indolopyrrolocarbazoles. EP 0971717; JP 2000516250; WO 9807433 .

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)	19711	1H-pyrrole-2,5-dione	541-59-3	C₄H₃NO₂	详情	详情
(II)	48178	3,4-dibromo-1H-pyrrole-2,5-dione		C₄HBr₂NO₂	详情	详情
(III)	20588	1-(bromomethyl)-4-(tert-butyl)benzene	18880-00-7	C₁₁H₁₅Br	详情	详情
(IV)	48179	3,4-dibromo-1-[4-(tert-butyl)benzyl]-1H-pyrrole-2,5-dione		C₁₅H₁₅Br₂NO₂	详情	详情
(V)	32388	5-Fluoroindole; 5-Fluoro-1H-indole	399-52-0	C₈H₆FN	详情	详情
(VI)	48180	1-[4-(tert-butyl)benzyl]-3,4-bis(5-fluoro-1H-indol-3-yl)-1H-pyrrole-2,5-dione		C₃₁H₂₅F₂N₃O₂	详情	详情
(VII)	48181	6-[4-(tert-butyl)benzyl]-3,9-difluoro-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione		C₃₁H₂₃F₂N₃O₂	详情	详情
(VIII)	48182	(3R,4R,5S,6R)-3,4-bis(benzyloxy)-6-[(benzyloxy)methyl]-5-fluorotetrahydro-2H-pyran-2-ol		C₂₇H₂₉FO₅	详情	详情
(IX)	48183	12-[(2R,3R,4R,5S,6R)-3,4-bis(benzyloxy)-6-[(benzyloxy)methyl]-5-fluorotetrahydro-2H-pyran-2-yl]-6-[4-(tert-butyl)benzyl]-3,9-difluoro-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione		C₅₈H₅₀F₃N₃O₆	详情	详情
(X)	48184	6-[4-(tert-butyl)benzyl]-3,9-difluoro-12-[(2R,3R,4R,5S,6R)-5-fluoro-3,4-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione		C₃₇H₃₂F₃N₃O₆	详情	详情

Extended Information