Imipenem intermediate and preparation method of imine peinan

A technology of imipenem and imipenem side chain, which is applied in the field of imipenem preparation, and can solve the problems of long synthetic route and high cost

Inactive Publication Date: 2007-04-18
安徽巴迪生物医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage is that the synthetic route is long and the cost is still high

Method used

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  • Imipenem intermediate and preparation method of imine peinan
  • Imipenem intermediate and preparation method of imine peinan
  • Imipenem intermediate and preparation method of imine peinan

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] [Example 1] N, N'-two [(N-p-nitrobenzyloxycarbonyl) imidoyl) cystamine N, the preparation of N'-Di(N-p-nitrobenzyloxycarbonyl) formimidoyl) cystamine:

[0035]

[0036] Under the protection of argon (or nitrogen) gas, 51.5 g (0.30 mol) of benzyl imidine ether hydrochloride and 100 ml of acetonitrile were added to form a suspension. A dry ice-ethanol bath cooled the reaction solution below -40°C, added 73.0g (98ml, 0.565mol) of diisopropylethylamine under stirring, then added 51.2g (0.238mol) of chloroformic acid at the same temperature to Nitrobenzyl ester is dissolved in the solution of 50ml acetonitrile, stirs 20min, the clear solution that obtains is the solution containing N-(p-nitrobenzyloxycarbonyl)-iminoformic acid benzyl ester (Benzyl (N-p-nitrobenzyloxycarbonyl) formimidate), as Reaction A.

[0037] In a 250ml single-necked bottle, add 26.7g (0.119mol) of cystamine dihydrochloride, then add 100ml of pyrrolidone and 31g (0.238mol) of diisopropylethylamine an...

Embodiment 2

[0044] [Example 2] N, N'-two [(N-benzyloxycarbonyl) iminomethylidene] cystamine N, the preparation of N'-Di((N-benzyloxycarbonyl) formimidoyl) cystamine:

[0045]

[0046] Except that the solution that the p-nitrobenzyl chloroformate that adds 51.2g (0.238mol) in embodiment 1 is dissolved in 50ml acetonitrile replaces the solution that the benzyl chloroformate that adds 40.6g (0.238mol) is dissolved in 50ml acetonitrile, other additions The amount and method are the same. Obtained N,N'-di[(N-benzyloxycarbonyl)iminomethylidene]cystamine [N,N'-Di((N-benzyloxycarbonyl)formimidoyl)cystamine]33.9g (yield 60%, content 96 %).

[0047] Mp: 120~122℃

[0048] Determination results of physical properties of the compound:

[0049] Ms: M+1=475

[0050] IR max KBr cm -1 : 1739, 1699, 1675, 1639, 1447, 1241, 1168, 761.

[0051] 1 H-NMR (δ, DMSO-d 6 ): 2.89 (4H, m, SCH 2 ), 3.55 (4H, m, NCH 2 ), 5.05 (4H, s, OCH 2 ), 7.34 (10H, m, ArH), 8.38 (2H, d, NCH=N).

[0052] 13 C-NMR...

Embodiment 3

[0053] [Example 3] N, N'-two [(N-allyloxycarbonyl) imidoyl] cystamine N, the preparation of N'-Di((N-allyloxycarbonyl) formimidoyl) cystamine:

[0054]

[0055] Except that the p-nitrobenzyl chloroformate that adds 51.2g (0.238mol) in embodiment 1 is dissolved in the solution of 50ml acetonitrile and replaces the solution that the allyl chloroformate of 28.7g (0.238mol) is dissolved in 50ml acetonitrile, other The dosage and method are the same. Obtained N, N'-bis[(N-allyloxycarbonyl)iminomethylidene]cystamine [N,N'-Di((N-allyloxycarbonyl)formimidoyl)cystamine] 33.4g (yield 75%, content 95%).

[0056] Mp: 108~110℃

[0057] Determination results of physical properties of the compound:

[0058] Ms: M+1=375

[0059] IR max KBr cm -1 : 1698, 1640, 1449, 1336, 1241, 1178, 1085, 983, 794.

[0060] 1 H-NMR (δ, DMSO-d 6 ): 2.91 (4H, m, SCH 2 ), 3.53 (4H, m, NCH 2 ), 4.50 (4H, d, OCH 2 ), 5.23 (4H, m, = CH 2 ), 5.91 (2H, m, -CH=), 8.35 (2H, d, NCH=N).

[0061] 13 C-N...

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Abstract

The present invention relates to a new intermediate compound for synthesizing imipenen. Said invention also provides the chemical structure formula of said intermediate compound. Besides, said invention also provides a method for preparing imipenen side chain and imipenen.

Description

technical field [0001] The present invention relates to a new intermediate compound (I) in the synthesis of N-thiamycin (imipenem) and a method for preparing imipenem. [0002] Background technique [0003] Imipenem is a well-known antibiotic, which has been reported in many patents and literatures, such as: USP4,292,436, 4,374,772, 2002 / 0095034 and Sletzinger et al., Tetrahedron Lett., 21, 4221-4224 (1980). [0004] [0005] There are currently three routes for the synthesis of imipenem: [0006] (1) MERCK&CO INC, US4292436, 1981-09-29 route: [0007] [0008] The advantage of this process is that the penem core and the imine side chain are condensed in one step, and the route is short and the yield is high. The disadvantage is that the protected imine side chain (VI) is very unstable and is easily decomposed under the conditions of air, water, acid and alkali, or changes to (VII) according to the following reaction structure. [0009] [0010] In practical o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C323/40C07F7/08C07D477/20
Inventor 张工张艳丽杨东
Owner 安徽巴迪生物医药科技有限公司
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