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PROCESS FOR PREPARING (2R,3S)-1-(4-AMINO-N-ISOBUTYLPHENYLSULFONAMIDO)-4-PHENYL-3-(((S)-TETRAHYDROFURAN-3-YLOXY)CARBONYLAMINO)BUTAN-2-YL PHOSPHATE

IP.com Disclosure Number: IPCOM000197718D
Publication Date: 2010-Jul-20
Document File: 2 page(s) / 27K

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The IP.com Prior Art Database

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         PROCESS FOR PREPARING (2R,3S)-1-(4-AMINO-N- ISOBUTYLPHENYLSULFONAMIDO)-4-PHENYL-3-(((S)-TETRAHYDROFURAN- 3-YLOXY)CARBONYLAMINO)BUTAN-2-YL PHOSPHATE

Route of synthesis:

HO

O

Me

Me

NO2

HO

P

NO2

OH

Me

O

H

N

N

  S
O O

1. POCl3, Py

2. HCl

HN N

Me

BOC

MIBIK

BOC

  S
O O

1 2

HCl

toluene

HO O

HO

Me

P

NO2

HO

O

Me

O

P

Me

NO2

  S
O O

1,1'-carbonyldiimidazole

(S)-3-tetrahydrofuranol

EtOAc

HO

HCl

O

HN N

Me

O

N

  S
O O

O

H2N

O

4

3

Pd/C, H2

EtOAc

HO O

HO

Me

P

NH2

O

  S
O O

O

HN N

Me

O

O

5

Example 1: Preparation of tert-butyl (2S,3R)-4-(N-isobutyl-4-nitrophenylsulfonamido)-1- phenyl-3-(phosphonooxy)butan-2-yl carbamate (2)

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Phosphorus oxychloride is added to the reactant (1) in the presence of pyridine as catalyst in methyl-isobutyl ketone as solvent. After the reaction is finished, the mixture is hydrolyzed with diluted hydrochloric and the product (2) is isolated from methyl isobutyl ketone.

Example 2: Deprotection of BOC protected intermediate (2) to prepare (2R,3S)-3-amino-1- (N-isobutyl-4-nitrophenylsulfonamido)-4-phenylbutan-2-yl dihydrogen phosphate hydrochloride (3)

BOC protecting group is removed by heating intermediate (2) in toluene with concentrated HCl which affords primary amine (3) in form of hydrochloric salt.

Example 3: Preparing of (R)-tetrahydrofuran-3-yl (2S,3R)-4-(N-isobutyl-4- nitrophenylsulfonamido)-1-phenyl-3-(phosphonooxy)butan-2-yl carbamate (4) Compound (3) is condensed with imidazole-1-carboxylic acid -3-(S)-tetrahydrofuryl ester (which is prepared by reac...