Preparation method of 1,2,3,4-tetrahydroisoquinoline derivative

A technology of tetrahydroisoquinoline and its derivatives, applied in organic chemistry and other fields, can solve problems such as limiting the scope of use of methods, and achieve the effects of low price, good tolerance, universal applicability, and reduced dosage

Active Publication Date: 2018-12-14
WUHAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of these methods require pre-synthesis of special functional groups, which greatly limits the scope of application of these methods

Method used

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  • Preparation method of 1,2,3,4-tetrahydroisoquinoline derivative
  • Preparation method of 1,2,3,4-tetrahydroisoquinoline derivative
  • Preparation method of 1,2,3,4-tetrahydroisoquinoline derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Embodiment 1: the preparation of compound I-1

[0039]

[0040] Under the protection of inert gas, add Pd(OAc) to a dry 4.0mL reaction bottle equipped with a magnetic stir bar 2 (4.6mg, 0.02mmol, 0.10eq), tris(furan-2-yl)phosphine (11.2mg, 0.048mmol, 0.24eq), 2-p-tolyl-3a,4,7,7a-tetrahydro-1H- 4,7-methyleneisoindole-1,3(2H)-dione (10.2mg, 0.04mmol, 0.20 equivalent), potassium carbonate (55.6mg, 0.4mmol, 2.0 equivalent), o-iodotoluene (52.3mg, 0.24mmol, 1.2eq), 1-p-toluenesulfonylaziridine (39.5mg, 0.2mmol, 1.0eq), ethyl acrylate (30.0mg, 0.3mmol, 1.5eq) and dry acetonitrile (1.0mL). The vial was capped and stirred at room temperature for about 5 minutes, after which the mixture was heated to 70°C and stirred for 16 hours. After the reaction vessel was cooled to room temperature, it was quenched with water (10 mL), extracted with ethyl acetate (3×10 mL), Na 2 SO 4 Dry, filter and concentrate in vacuo. Purified by column chromatography, the eluent was petroleum et...

Embodiment 2

[0041] Embodiment 2: the preparation of compound 1-2

[0042]

[0043] The aryl iodide used was 2-ethyliodobenzene (55.7 mg, 0.24 mmol), and other conditions were the same as in Example 1 to obtain compound I-2 (colorless oily liquid, yield 84%). 1 H NMR (400MHz, CDCl 3 ):δ 7.58–7.56(m,2H),7.11–7.01(m,4H),6.77(dd,J=7.5,1.5Hz,1H),5.66(dd,J=10.1,3.8Hz,1H),4.13 (qd,J=7.2,2.6Hz,2H),3.78–3.63(m,2H),2.81–2.69(m,4H),2.65–2.56(m,2H),2.32(s,3H),1.29–1.24 (m,6H). 13 C NMR (100MHz, CDCl 3 ): δ170.23, 143.22, 139.98, 137.28, 133.52, 133.15, 129.40, 127.42, 127.28, 126.85, 126.81, 61.13, 51.09, 42.01, 39.10, 26.77, 24.43, 21.536, 15. Calculated value: C 22 h 27 NaNSO 4 [M+Na + ] 424.1553, measured value: 424.1556.

Embodiment 3

[0044] Embodiment 3: the preparation of compound 1-3

[0045]

[0046] The aryl iodide used was 2-isopropyl iodobenzene (59.1 mg, 0.24 mmol), and other conditions were the same as in Example 1 to obtain compound I-3 (colorless oily liquid, yield 86%). 1 H NMR (400MHz, CDCl 3 ): δ 7.59–7.56(m,2H),7.13–7.07(m,4H),6.74(dd,J=6.4,2.4Hz,1H),5.73(dd,J=10.3,3.9Hz,1H),4.19 –4.11(m,2H),3.76–3.67(m,2H),3.23–3.17(m,1H),2.80 (dd,J=14.6,10.2Hz,1H),2.73–2.69(m,2H),2.55 (dd,J=14.6,3.9Hz,1H),2.31(s,3H),1.30–1.24(m,6H),1.22(d,J=6.7Hz,3H). 13 C NMR (100MHz, CDCl 3):δ 170.13,144.97,143.19,137.34,133.00,132.57,129.38,127.57,127.27,126.79, 124.01,61.12,50.97,42.49,38.98,27.90,26.87,25.26,23.49,21.54,14.29.HRMS (ESI-TOF ): Theoretical calculation value: C 23 h 29 NaNSO 4 [M+Na + ] 438.1710, measured value: 438.1712.

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Abstract

The invention discloses a preparation method of a 1,2,3,4-tetrahydroisoquinoline derivative. Aromatic iodide, aziridine compounds and olefin compounds are used as initial materials and stirred to react at 30-120 DEG C under the action of a catalyst, a ligand, a norbornene derivative and alkali, separation and purification are performed after the reaction, and the 1,2,3,4-tetrahydroisoquinoline derivative can be obtained. The 1,2,3,4-tetrahydroisoquinoline derivative can be synthesized efficiently, economically and greenly with the method. The method is mild in condition, good in substrate universality and high in yield, and the prepared 1,2,3,4-tetrahydroisoquinoline derivative can be widely applied to the fields of medicinal chemistry and organic chemistry.

Description

technical field [0001] The invention belongs to the field of organic synthesis or medicinal chemistry, and specifically relates to a preparation method of 1,2,3,4-tetrahydroisoquinoline derivatives. Background technique [0002] The 1,2,3,4-tetrahydroisoquinoline skeleton with multifunctional substitution is an important class of structural units, which widely exist in biologically active natural products and pharmaceutical reagents ([1]M.E.Zarranz De Ysern,L . Prog.Neuro-Psychopharmacol,1981,5,343.[2]J.D.Scott,R.M.Williams,Chem.Rev.2002,102,1669.[3]V.G.Kartsev,Med.Chem.Res.2004,13,325.[4] K.W.Bentley, Nat.Prod.Rep.2006,23,444.[5]N.Cabedo,I.Berenguer,B.Figadere,D.Cortes,Curr.Med.Chem.2009,16,2441.[6]P.Zhu , W. Ye, J. Li, Y. Zhang, W. Huang, M. Cheng, Y. Wang, Y. Zhang, H. Liu, J. Zuo, Chem. Biol. Drug Des. 2017, 89, 443. [7 ]K.Fujimoto,T.Oka,M.Morimoto,Cancer Res.1987,47,1516.[8]R.Kanamaru,Y.Konishi,C.Ishioka,H.Kakuta,T.Sato,A.Ishikawa,M .Asamura,A.Wakui,Cancer Chemothe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D217/14C07D221/10C07D491/056C07D471/04C07D405/06
CPCC07D217/14C07D221/10C07D405/06C07D471/04C07D491/056
Inventor 周强辉钱光印白淼
Owner WUHAN UNIV
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