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A process for the preparation of (3R)-3-amino-1-[9-(trifluoromethyl)-1,4,7,8-tetrazabicyclo[4.3.0]nona-6,8-dien-4-yl]-4-(2,4,5- trifluorophenyl)butan-1-one

IP.com Disclosure Number: IPCOM000200350D
Publication Date: 2010-Oct-07
Document File: 2 page(s) / 17K

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The IP.com Prior Art Database

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A process for the preparation of (3R)-3-amino-1-[9-(trifluoromethyl)-1,4,7,8- tetrazabicyclo[4.3.0]nona-6,8-dien-4-yl]-4-(2,4,5- trifluorophenyl)butan-1-one

(3R)-3-amino-1-[9-(trifluoromethyl)-1,4,7,8-tetrazabicyclo[4.3.0]nona-6,8-dien-4-yl]-4- (2,4,5- trifluorophenyl)butan-1-one, has the following chemical structure:

F

F

The phosphate salt of (3R)-3-amino-1-[9-(trifluoromethyl)-1,4,7,8- tetrazabicyclo[4.3.0]nona-6,8-dien-4-yl]-4-(2,4,5- trifluorophenyl)butan-1-one is a glucagon-like peptide 1 metabolism modulator, hypoglycemic agent, and dipeptidyl peptidase IV inhibitor.

The synthesis of (3R)-3-amino-1-[9-(trifluoromethyl)-1,4,7,8-tetrazabicyclo[4.3.0]nona- 6,8-dien-4-yl]-4-(2,4,5- trifluorophenyl)butan-1-one is described in the literature (WO 2004/085378, WO2005/097733 ) by hydrogenated of (Z)-3-amino-1-(3-(trifluoromethyl)- 5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-2-en-1- one in the presence of asymmetric homogenous catalyst.

Provided is a process, based on the procedure described in K.B. Hansen et al., Organic letter, 2005, vol 7(2) 4935-4938, using an anhydride (preferably, the anhydride is BOC anhydride). After hydrogenation the reaction mixture contains a mixture of protected and non-protected product.

F

NH2 O

N

N

N N

CF

3


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The protected group can be removed by any known procedure for the protecting group removal, for example, in acidic conditions as by trifluoroacetic acid, HCl or H3PO4 in different solvents as alcohols, ethers, or esters with or without water.

Example

A 1L hydrogenation reactor was l...