1-[7-bromo-3,4-dihydro-2(1H)-isoquinolinyl]-2,2,2-trifluoro-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】33024

【品名】1-[7-bromo-3,4-dihydro-2(1H)-isoquinolinyl]-2,2,2-trifluoro-1-ethanone

【CA登记号】

【分子式】C₁₁H₉BrF₃NO

【分子量】308.0978096

【元素组成】C 42.88% H 2.94% Br 25.93% F 18.5% N 4.55% O 5.19%

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：(II)

Tetrahydroisoquinoline (II) was prepared by intramolecular cyclization of N-trifluoroacetyl 4-bromophenethylamine (I) with paraformaldehyde in acetic/ sulfuric acid. Displacement of the bromine atom of (II) with CuCN in boiling N-methyl-2-pyrrolidinone produced nitrile (III). The trifluoroacetyl group og (III) was then removed by means of K2CO3 in aqueous methanol, yielding the intermediate isoquinoline (IV).

参考文献中间体

合成目标

【1】 Stokker, G.E.; Preparation of 1,2,3,4-tetrahydroisoquinolines lacking electron donating groups - an intramolecular cyclization complementary to the Pictet-Spengler reaction. Tetrahedron Lett 1996, 37, 31, 5453.
【2】 Branch, C.L.; Stemp, G.; Johnson, C.N. (SmithKline Beecham plc); Tetrahydroisoquinoline derivs. as modulators of dopamine D3 receptors. EP 0983244; WO 9850364 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	33023	N-(4-bromophenethyl)-2,2,2-trifluoroacetamide	C₁₀H₉BrF₃NO	详情	详情
(II)	33024	1-[7-bromo-3,4-dihydro-2(1H)-isoquinolinyl]-2,2,2-trifluoro-1-ethanone	C₁₁H₉BrF₃NO	详情	详情
(III)	33025	2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydro-7-isoquinolinecarbonitrile	C₁₂H₉F₃N₂O	详情	详情
(IV)	33026	1,2,3,4-tetrahydro-7-isoquinolinecarbonitrile	C₁₀H₁₀N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Bromoisoquinoline (I) was converted into stannane (II) upon treatment with hexabutylditin in the presence of palladium catalyst. Subsequent Stille coupling of (II) with chloroquinolizinone (III) provided adduct (IV). Then, basic hydrolysis of both ethyl ester and trifluoroacetamide groups afforded the target compound, which was finally converted to the hydrochloride salt.

参考文献中间体

合成目标

【1】 Bui, M.; Nilius, A.; Nan, Y.; Marron, T.; Stone, G.; Baranowski, J.; Shen, L.; Schultz, C.C.; Raney, P.; Snyder, R.; Or, Y.S.; Synthesis and antibacterial activity of C-8 carbon-linked 2-pyridones. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F560.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	33024	1-[7-bromo-3,4-dihydro-2(1H)-isoquinolinyl]-2,2,2-trifluoro-1-ethanone	C₁₁H₉BrF₃NO	详情	详情
(II)	38122	2,2,2-trifluoro-1-[7-(tributylstannyl)-3,4-dihydro-2(1H)-isoquinolinyl]-1-ethanone	C₂₃H₃₆F₃NOSn	详情	详情
(III)	16831	ethyl 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylate	C₁₆H₁₅ClFNO₃	详情	详情
(IV)	38123	ethyl 1-cyclopropyl-7-fluoro-9-methyl-4-oxo-8-[2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydro-7-isoquinolinyl]-4H-quinolizine-3-carboxylate	C₂₇H₂₄F₄N₂O₄	详情	详情

Extended Information