5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole -Drug Synthesis Database

【结构式】

【分子编号】16719

【品名】5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole

【CA登记号】116673-95-1

【分子式】C₁₃H₁₇N

【分子量】187.28472

【元素组成】C 83.37% H 9.15% N 7.48%

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：(I)

The cyclization of 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (I) with 4-chlorophenacyl bromide (II) ethyl ether/ethanol gives 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (III), which is condensed with ethyl diazoacetate (IV) by means of copper powder in refluxing toluene to afford 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid ethyl ester (V). Finally, this ester is hydrolyzed with NaOH in ethanol/water.

参考文献中间体

合成目标

【1】 Rabasseda, X.; Mealy, N.; Castañer, J.; ML-3000. Drugs Fut 1995, 20, 10, 1007.
【2】 Augustin, J.; Kiefer, W.; Dannhardt, G.; Laufer, S.A.; (6,7-Diaryldihydropyrrolizin-5-yl)acetic acids, a novel class of potent dual inhibitors of both cyclooxygenase and 5-lipoxygenase. J Med Chem 1994, 37, 12, 1894-7.

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)	16719	5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole	116673-95-1	C₁₃H₁₇N	详情	详情
(II)	16720	2-bromo-1-(4-chlorophenyl)-1-ethanone; 2-Bromo-4'-chloroacetophenone	536-38-9	C₈H₆BrClO	详情	详情
(III)	16721	6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine		C₂₁H₂₀ClN	详情	详情
(IV)	15911	Ethyldiazoacetate; ethyl 2-diazoacetate	623-73-4	C₄H₆N₂O₂	详情	详情
(V)	16723	ethyl 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetate		C₂₅H₂₆ClNO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The cyclization of 4-chloro-3,3-dimethylbutyronitrile (I) with benzylmagnesium chloride (II) in ethyl ether containing some iodine gives 2-benzyl-4,4-dimethyl-1-pyrroline (III), which is cyclized with 4'-chlorophenacyl bromide (IV) by means of NaHCO3 in methanol, yielding 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro.1H-pyrrolizine (V). The condensation of (V) with oxalyl chloride (VI) in THF affords 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]-2-oxoacetyl chloride (VII), which is finally reduced and hydrolyzed with hydrazine in hot diethyleneglycol to provide the target licofelone.

参考文献中间体

合成目标

【1】 Laufer, S.; Striegel, H.-G.; Kammermeier, T.; Merckle, P. (Merckle GmbH); Method for producing 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl acetic acid. US 6417371; WO 0155149 .

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)	60052	4-chloro-3,3-dimethylbutanenitrile		C₆H₁₀ClN	详情	详情
(II)	18327	benzyl(chloro)magnesium	6921-34-2	C₇H₇ClMg	详情	详情
(III)	16719	5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole	116673-95-1	C₁₃H₁₇N	详情	详情
(IV)	16720	2-bromo-1-(4-chlorophenyl)-1-ethanone; 2-Bromo-4'-chloroacetophenone	536-38-9	C₈H₆BrClO	详情	详情
(V)	16721	6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine		C₂₁H₂₀ClN	详情	详情
(VI)	29841	Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride	79-37-8	C₂Cl₂O₂	详情	详情
(VII)	60053	2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]-2-oxoacetyl chloride		C₂₃H₁₉Cl₂NO₂	详情	详情

Extended Information