Synthetic method of famciclovir intermediate

A technology of famciclovir intermediate and synthetic method, which is applied in the field of synthesis of famciclovir intermediate, can solve the problems of low total yield, long reaction steps, and reduced product purity, and achieve the effects of high yield, few steps, and reduced production cost

Inactive Publication Date: 2013-02-13
CHONGQING SHENGHUAXI PHARMA CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But this patent reaction step is long, and total yield is low, and bromination reaction needs to use expensive carbon tetrabromide, and 2-amino-9-bromoethyl purine is unstable, can self-condense (as follows), reduces product purity

Method used

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  • Synthetic method of famciclovir intermediate
  • Synthetic method of famciclovir intermediate
  • Synthetic method of famciclovir intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Dissolve 50g (0.259mol) of 2,4-dichloro-5-nitropyrimidine in 600ml of ethanol, stir at 20-30°C, then add 46.5g (0.390mol) of 2-(2-aminoethyl)propanediol and 41g of sodium carbonate , reacted at 50-60°C for 12 hours, filtered while it was hot, cooled the filtrate to 0-10°C, and gradually precipitated light yellow crystals, filtered to obtain 2-{2-[(2-chloro-5-nitropyrimidin-4-yl ) amino] ethyl}-1,3-propanediol 56g, yield 78%.

Embodiment 2

[0034] Dissolve 30g (0.109mol) of 2-{2-[(2-chloro-5-nitropyrimidin-4-yl)amino]ethyl}-1,3-propanediol in 300ml of methanol, stir at 30-40°C, and pass through Add ammonia gas for ammonolysis for 15 hours, cool at 0-10°C, stir for 4 hours, filter the precipitated light yellow crystals to obtain 2-{2-[(2-amino-5-nitropyrimidin-4-yl)amino]ethyl Base}-1,3-propanediol 24g, yield 86%.

Embodiment 3

[0036] Mix 40g (0.156mol) of 2-{2-[(2-amino-5-nitropyrimidin-4-yl)amino]ethyl}-1,3-propanediol with 600ml of ethanol, stir and dissolve at 30-40℃, then Add 5 g of 10% palladium carbon, hydrogenate under normal pressure for 10 hours, filter, and concentrate the filtrate to remove the solvent to obtain 2-{2-[(2-amino-5-aminopyrimidin-4-yl)amino]ethyl}-1 , 35g (theoretical amount) of 3-propanediol does not need to be purified and can be directly used in the cyclization reaction.

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Abstract

A synthetic method of a famciclovir intermediate comprises the following steps: carrying out a condensation of an initial raw material 2,4-dichloro-5-nitropyrimidine and 2-(2-aminoethyl)propylene glycol, carrying out selective substitution of the 4th chlorine atom to obtain 2-{2-[(2-chloro-5-nitropyrimidyl-4-yl)amino]ethyl}-1,3-propylene glycol, and ammonolyzing to obtain 2-{2-[(2-amino-5-nitropyrimidyl-4-yl)amino]ethyl}-1,3-propylene glycol; and further reducing to obtain 2-{2-[(2-amino-5-aminopyrimidyl-4-yl)amino]ethyl}-1,3-propylene glycol, and cyclizing to obtain the famciclovir intermediate 2-[2-(2-amino-9H-purine-9-yl)ethyl]-1,3-propylene glycol. The synthetic method has the advantages of less steps, high yield, effective avoiding of the generation of isomers, simple subsequent purification step, production cost reduction, and suitableness for the industrialized application.

Description

technical field [0001] The invention relates to a synthetic method of a famciclovir intermediate. Background technique [0002] Famciclovir is a second-generation ring-opening nucleoside anti-herpes virus drug developed by SmithKline Beecham Pharmaceutical Company of the United Kingdom. It is also the first oral drug approved for cold sores and genital herpes in the United States. Famciclovir is a purine derivative. There are many synthetic routes reported in the literature. In summary, purine derivatives are used as the parent ring, condensed with different side chains to obtain the basic structure of famciclovir, and then the positioning substituents on the parent ring are removed. Or further structural modification on the side chain to obtain famciclovir. [0003] The famciclovir synthesis method was first seen in patents WO8705604 and EP141927, and the famciclovir synthesis route described in this patent is as follows: [0004] [0005] When preparing intermediate ...

Claims

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Application Information

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IPC IPC(8): C07D473/32
Inventor 姜维平何亮周艳婷
Owner CHONGQING SHENGHUAXI PHARMA CO LTD
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