A kind of preparation method of tetrahydro-1,5-naphthyridine compound and chiral product obtained therefrom

The technology of a compound, naphthyridine, is applied in the field of preparation of tetrahydro-1,5-naphthyridine compounds and the chiral products prepared therefrom, and can solve problems such as catalyst poisoning

Active Publication Date: 2017-04-05
INST OF CHEM CHINESE ACAD OF SCI
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Problems solved by technology

However, the asymmetric hydrogenation of polyaromatic heterocyclic compounds containing multiple heteroatoms still faces great challenges, mainly because polyaromatic heterocyclic compounds not only have very stable conjugated structures, but also have multiple Heteroatoms that can coordinate with transition metals have stronger coordination ability than simple aromatic heterocycles and are more likely to cause catalyst poisoning

Method used

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  • A kind of preparation method of tetrahydro-1,5-naphthyridine compound and chiral product obtained therefrom
  • A kind of preparation method of tetrahydro-1,5-naphthyridine compound and chiral product obtained therefrom
  • A kind of preparation method of tetrahydro-1,5-naphthyridine compound and chiral product obtained therefrom

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preparation example Construction

[0020] The present invention provides a method for preparing tetrahydro-1,5-naphthyridine compounds, wherein the method comprises: in the presence of a chiral catalyst, performing an addition reaction of a compound represented by formula (1) with hydrogen, wherein , the chiral catalyst is a complex of the structure shown in formula (2);

[0021]

[0022] Among them, R 1 , R 2 and R 3 each independently hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted arylbenzyl base, or R 1 and R 3 Connect to form a C5-C8 membered alkane ring, wherein, the substituents in the substituted alkyl, substituted cycloalkyl, substituted aryl and substituted arylbenzyl are each independently selected from fluorine, chlorine, bromine, nitro One or more of radical, methyl, methoxy, trifluoromethyl, hydroxyl and acetamido; and, R 1 not hydrogen;

[0023]

[0024] Wherein, M i...

preparation example 1

[0138] (1) Dissolve (R,R)-1,2-diphenyl-ethylenediamine (20mmol, purchased from Bailingwei Technology Co., Ltd. 24694 brand) in dichloromethane (30mL), and dissolve in P-methylphenylsulfonyl chloride (20mmol, purchased from Bailingwei Technology Co., Ltd. 283322 brand) in dichloroethane (30mL) was added dropwise (dropped within 30min), continued to react at 0°C for 1h, and then reduced pressure Rotary evaporation, the solid was separated and purified by column chromatography (the eluent was dichloromethane / methanol with a volume ratio of 10:1), so as to obtain 15 mmol of the formula (R, R)-(3-1-1-1) The chiral diamine shown has a yield of 75%, and the identification data of this chiral diamine is: 1 H NMR (300MHz, CDCl 3 ): δ7.31(d, J=8.3Hz, 2H), 7.18-7.09(m, 10H), 6.97(d, J=8.3Hz, 2H), 4.37(d, J=5.2Hz, 1H), 4.12 (d,J=5.2Hz,1H),2.32(s,3H),1.49(br,3H); 13 C NMR (75MHz, CDCl 3 ): δ142.5, 139.2, 137.2, 129.1, 128.4, 128.2, 127.5, 127.4, 127.0, 126.9, 126.6, 63.2, 60.5, 21.4. ...

preparation example 2

[0142] (1) According to the method of step (1) in Preparation Example 1, the difference is that methanesulfonyl chloride (20mmol, purchased from Alfa Aisha Chemical Co., Ltd. A13383 brand) is used instead of p-methylphenylsulfonyl chloride, and Reaction at 0°C for 1 h, thereby obtaining 14.6 mmol of chiral diamine represented by the formula (R,R)-(3-1-1-2), with a yield of 73%. The identification data of the chiral diamine for: 1 H NMR (300MHz, CDCl 3 ): δ7.34-7.26(m, 10H), 4.56(d, J=5.1Hz, 2H), 4.21(d, J=5.1Hz, 2H), 2.26(s, 3H); 13 C NMR (75MHz, CDCl 3 ): δ141.9, 139.7, 128.7, 128.6, 127.9, 127.8, 126.9, 126.7, 63.4, 60.2, 40.7.

[0143] (2) According to the method of step (2) in Preparation Example 1, the difference is that the chiral diamine used is the chiral diamine shown in the above formula (R, R)-(3-1-1-2) (145 mg, 0.5 mmol), recrystallized to obtain 275 mg of a red solid (ie, the complex shown in formula (R, R)-4j);

[0144] (3) According to the method of step (3...

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Abstract

The invention discloses a method for preparing a tetrahydro-1,5-naphthyridine compound. The method comprises the following steps: carrying out an addition reaction between a compound with the structure shown as a formula (1) and hydrogen in the presence of a chiral catalyst, wherein the chiral catalyst is a coordination complex with a structure shown as a formula (2). The invention also provides a chiral product of the tetrahydro-1,5-naphthyridine compound prepared by the method. The proper compound with the structure shown as the formula (1) is selected as a substrate, the proper coordination complex with the structure shown as the formula (2) is selected as the chiral catalyst, and selective hydrogenation reduction of the 1,5-naphthyridine compound with the structure shown as the formula (1) is realized by adopting hydrogen, so that the chiral product of the tetrahydro-1,5-naphthyridine compound is prepared at low cost. The chiral product of the tetrahydro-1,5-naphthyridine compound prepared by the invention can serve as a structure block of bioactive compounds and chiral drugs.

Description

technical field [0001] The invention relates to a preparation method of tetrahydro-1,5-naphthyridine compounds and the prepared chiral products. Background technique [0002] At present, the R&D, production and sales of chiral drugs have become the mainstream of the development of the global pharmaceutical industry (A.M.Rouhi, "Chiral Chemistry", Chem. Eng. News 2004, 82, 47). Chiral heterocyclic compounds are the skeleton structures of many biologically active compounds and chiral drugs, and have high research value and application prospects. The high-efficiency asymmetric synthesis of chiral heterocyclic compounds has attracted great attention from the pharmaceutical community and organic synthetic chemists, and a variety of asymmetric synthetic methods have been reported. Among them, chiral heterocyclic compounds are prepared by asymmetric catalytic hydrogenation of aromatic heterocyclic compounds. Sexual heterocyclic compounds are one of the most atom-economical and eff...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D471/04B01J31/22
CPCB01J31/2295B01J2231/646B01J2531/004C07D471/04
Inventor 范青华张建伟陈飞何艳梅
Owner INST OF CHEM CHINESE ACAD OF SCI
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