4-(bromomethyl)-1,1'-biphenyl -Drug Synthesis Database

【结构式】

【分子编号】31210

【品名】4-(bromomethyl)-1,1'-biphenyl

【CA登记号】2567-29-5

【分子式】C₁₃H₁₁Br

【分子量】247.13434

【元素组成】C 63.18% H 4.49% Br 32.33%

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：(B)

Resolution of bicyclo[3.2.0]hept-2-en-6-one (I) via the R-(+)-alpha-methylbenzylamine-bisulfite (A) addition complex provides the 1S-(-)-enantiomer (II), which affords the 3-endo-acetoxy-2-exo-bromobicyclo[3.2.0]heptan-6-one (III) on treatment with 1,3-dibromo-5,5-dimethylhydantoin (DBDMH). Reaction with piperidine followed by hydrolysis gives the hydroxynorbornanone (IV), which is alkylated with biphenylmethylbromide (B) under phase-transfer catalysis to yield the norbornanone (V). Baeyer-Villiger oxidation followed by partial reduction with diisobutylaluminum hydride (Dibal) gives the aldehyde (VII), which is then homologated to the aldehyde (VIII) using methoxymethylene-phosphorane and subsequent treatment with 2N HCl. Condensation of (VIII) with carboxypropyltriphenylphosphorane in tetrahydrofuran followed by esterification with tritylchloride gives the ester (IX). The alcohol stereochemistry in (IX) is inverted via oxidation with pyridine-sulfur trioxide complex in dimethylsulfoxide followed by reduction with Dibal in the presence of 2,6-di-tert-butyl-4-methylphenol. Finally, the ester is hydrolyzed with hydrochloric acid to give the required acid.

参考文献中间体

合成目标

【1】 Coleman, M.J.; et al.; Baeyer-villiger oxidation of 5-endo-(biphenyl-4-ylmethoxy)-7-anti-piperidinobicyclo[2.2.1] process development and scale-Up. Org Process Res Dev 1997, 1, 1, 20.
【2】 Lumley, P.; Finch, H.; Collington, E.W.C.; Humphrey, P.P.A.; VAPIPROST HYDROCHLORIDE < Rec INNM; BAN >. Drugs Fut 1990, 15, 11, 1087.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	37404	(3-carboxypropyl)(triphenyl)phosphonium bromide	17857-14-6	C₂₂H₂₂BrO₂P	详情	详情
(A)	15148	1-phenylethylamine; DL-a-methylbenzylamine; 1-phenyl-1-ethanamine	618-36-0	C₈H₁₁N	详情	详情
(I), (II)	24421	(1S,5R)bicyclo[3.2.0]hept-2-en-6-one		C₇H₈O	详情	详情
(B)	31210	4-(bromomethyl)-1,1'-biphenyl	2567-29-5	C₁₃H₁₁Br	详情	详情
(III)	31208	(1R,2S,3S,5R)-2-bromo-6-oxobicyclo[3.2.0]hept-3-yl acetate		C₉H₁₁BrO₃	详情	详情
(IV)	31209	5-hydroxy-7-(1-piperidinyl)bicyclo[2.2.1]heptan-2-one		C₁₂H₁₉NO₂	详情	详情
(V)	31211	5-([1,1'-biphenyl]-4-ylmethoxy)-7-(1-piperidinyl)bicyclo[2.2.1]heptan-2-one		C₂₅H₂₉NO₂	详情	详情
(VI)	31212	6-([1,1'-biphenyl]-4-ylmethoxy)-8-(1-piperidinyl)-2-oxabicyclo[3.2.1]octan-3-one		C₂₅H₂₉NO₃	详情	详情
(VII)	31213	2-[(1R,2R,3R,5S)-5-([1,1'-biphenyl]-4-ylmethoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl]acetaldehyde		C₂₅H₃₁NO₃	详情	详情
(VIII)	31214	3-[(1R,2R,3R,5S)-5-([1,1'-biphenyl]-4-ylmethoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl]propanal		C₂₆H₃₃NO₃	详情	详情
(IX)	31215	trityl (Z)-7-[(1R,2R,3R,5S)-5-([1,1'-biphenyl]-4-ylmethoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-heptenoate		C₄₉H₅₃NO₄	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 2-(Boc-amino)caprolactam (I) with 4-(bromomethyl)biphenyl (II) in the presence of KOH and tetrabutylammonium iodide produced the N-(biphenylylmethyl) lactam (III). After Boc group cleavage with trifluoroacetic acid, the resulting amino lactam (IV) was coupled with the tyrosine derivative (V) using BOP to furnish the corresponding amide.

参考文献中间体

合成目标

【1】 Mandine, E.; Baholet, I.; Deprez, P.; et al.; SAR and rational design of Src SH2 binders around a heterocyclic scaffold identification of RU84687, a subnanomolar and Src SH2 selective binder. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PA-17.

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)	42810	L-(-)-N-alpha-Boc-amino-epsilon-caprolactam; tert-butyl (3S)-2-oxoazepanylcarbamate	76944-95-1	C₁₁H₂₀N₂O₃	详情	详情
(II)	31210	4-(bromomethyl)-1,1'-biphenyl	2567-29-5	C₁₃H₁₁Br	详情	详情
(III)	44317	tert-butyl (3S)-1-([1,1'-biphenyl]-4-ylmethyl)-2-oxoazepanylcarbamate		C₂₄H₃₀N₂O₃	详情	详情
(IV)	44318	(3S)-3-amino-1-([1,1'-biphenyl]-4-ylmethyl)-2-azepanone		C₁₉H₂₂N₂O	详情	详情
(V)	44319	(2S)-2-(acetamido)-3-[3-formyl-4-(phosphonooxy)phenyl]propionic acid		C₁₂H₁₄NO₈P	详情	详情

Extended Information