5-(3-bromopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene -Drug Synthesis Database

【结构式】

【分子编号】52139

【品名】5-(3-bromopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene

【CA登记号】

【分子式】C₁₈H₁₇Br

【分子量】313.23698

【元素组成】C 69.02% H 5.47% Br 25.51%

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)

Addition of cyclopropylmagnesium bromide (II) to dibenzocycloheptanone (I) afforded the carbinol adduct (III), which was further rearranged to the bromopropylidene derivative (IV) upon treatment with bromotrimethylsilane. Alkylation of ethyl (R)-nipecotate (V) with bromide (IV) gave the tertiary amine (VI). The ethyl ester group of (VI) was finally hydrolyzed under basic conditions to furnish the corresponding carboxylic acid.

参考文献中间体

合成目标

【1】 Andersen, K.E.; Olsen, U.B.; Petersen, H.; Grønvald, F.C.; Sonnewald, U.; Jørgensen, T.K.; Andersen, H.S. (Novo Nordisk A/S); Novel heterocyclic cpds.. US 5595989; US 5668129; US 5688788; US 5693649; US 5712292; US 5721254; US 5795888; US 6043239; WO 9518793 .
【2】 Olsen, U.B. (Novo Nordisk A/S); Novel method. JP 1999507947; WO 9722338 .

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)	40123	10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one; Dibenzosuberone	1210-35-1	C₁₅H₁₂O	详情	详情
(II)	12450	Bromo(cyclopropyl)magnesium;cyclopropylmagnesium bromide;cyclopropylmagnesiumbromide	23719-80-4	C₃H₅BrMg	详情	详情
(III)	52138	5-cyclopropyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ol		C₁₈H₁₈O	详情	详情
(IV)	52139	5-(3-bromopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene		C₁₈H₁₇Br	详情	详情
(V)	35224	ethyl (3S)-3-piperidinecarboxylate		C₈H₁₅NO₂	详情	详情
(VI)	52140	ethyl (3R)-1-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-3-piperidinecarboxylate		C₂₆H₃₁NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The condensation of dibenzocycloheptylidene derivative (I) with radiolabelled piperidine-3-carboxylic acid ethyl ester (II) by means of K2CO3 in ethyl acetate gives the adduct (III), which is hydrolyzed with aqueous HCl to yield the carboxylic acid (IV). Finally, this compound is submitted to optical resolution by means of chiral chromatography to provide the chiral radiolabelled compound.

参考文献中间体

合成目标

【1】 Valsborg, J.S.; Foged, C.; Radiolabelling of NNC 05-1869, a compound for treatment of diabetic neuropathy. J Label Compd Radiopharm 2002, 45, 4, 351.

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)	52139	5-(3-bromopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene		C₁₈H₁₇Br	详情	详情
(II)	25693	ethyl 3-piperidinecarboxylate	5006-62-2	C₈H₁₅NO₂	详情	详情
(II)	58262	ethyl 3-piperidinecarboxylate		C₈H₁₅NO₂	详情	详情
(III)	58263	ethyl 1-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-3-piperidinecarboxylate		C₂₆H₃₁NO₂	详情	详情
(III)	58266	ethyl 1-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-3-piperidinecarboxylate		C₂₆H₃₁NO₂	详情	详情
(IV)	58264	1-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-3-piperidinecarboxylic acid		C₂₄H₂₇NO₂	详情	详情
(IV)	58265	1-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-3-piperidinecarboxylic acid		C₂₄H₂₇NO₂	详情	详情

Extended Information