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9-(4-acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-chloropurine (Chloro FMC)

IP.com Disclosure Number: IPCOM000131141D
Publication Date: 2005-Nov-08
Document File: 2 page(s) / 70K

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  9-(4-acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-chloropurine (Chloro FMC) _______________________________________________________________________

Background: 9-(4-acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-chloropurine (Chloro FMC) is used as intermediate in the preparation of FMC. Its chemical formula is:

Cl

N

N

CH3

CH3

O

N

N

O

H2N

O

O

Chloro - FMC

Cl

N

N

N

N

N

N

O

N

N

H2N

H2N

CH3

CH3

CH3

CH3

O

O

O

O

O

O

O

Chloro - FMC FMC

WO 95/28402 discloses the preparation of Chloro FMC according to the following scheme:

Cl

H2N H

Cl

N

N

N

             K2CO3 (EtO2C)3CCH2CH2Br +

N

DMF

N

N

+

N

H2N

N

(EtO2C)3C

       CH3OH NaOCH3

Cl

Cl

N

N

N

N

N

N

N

N

1)NaBH4

H2N

(AcOCH2)2CH

H2N

(CH3O2C)2CH

2)Ac2O

DMAP

U.S. Patent No. 5,684,153 also discloses the preparation of Chloro FMC according to the following scheme:

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Cl

Cl

        NH2 H

LCH2CH2CH(CH2OAc)2

N

N

N

+

N

N

NH2

N

L= Br or I

N

N

OAc

OAc

Process description: Chloro FMC can be produced according to the following scheme:

Cl

Cl

N

N

N

+ CH2(COOEt)2 NaOMe

N

N

N

H2N CH2CH2Br

N

MeOH

H2N

N

(EtO2C)2CH

1. NaBH4

2. Ac2O

Cl

N

N

N

H2N

N

(AcOCH2)2CH .

The process comprises: condensation of 2-Amino-9-(2-bromoethyl)-6-Chloropurine with Diethyl malonate or Methyl malonate, under basic conditions, to obtain 2-Amino-9-(ethyl-2- carboethoxybutanoate-4-yl)-6-chloropurine, reduction of the 2-Amino-9-(ethyl-2- carboethoxybutanoate-4-yl)-6-chloropurine with Sodium borohydride to obtain 2-Amino-9-(4- hydroxy-3-hydr...