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Preparation of (R)-8-(3-amino-piperidin-1-yl)-7-(but-2-ynyl)-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione

IP.com Disclosure Number: IPCOM000238136D
Publication Date: 2014-Aug-05
Document File: 3 page(s) / 40K

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Preparation of (R)-8-(3-amino-piperidin-1-yl)-7-(but-2-ynyl)-3-methyl-1- (4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione


(R)-8-(3-amino-piperidin-1-yl)-7-(but-2-ynyl)-3-methyl-1-(4-methyl-quinazolin-2- ylmethyl)-3,7-dihydro-purine-2,6-dione (referred herein as Compound I) has the following chemical structure:

N

O

N

N

N

O N

N N

NH2

(I)

A process for the preparation of compound I was described in IPCOM000215450D. More recent publication (J.-jia Jin et al.; Tetrahedron, 69 (2013), 6579-6584) described that 2-methyl azaarene structure having activated C-H bond in the presence of acidic catalyst can react with aromatic aldehydes to give 1,3-di(2-quinolyl)propane derivatives through tandem C(sp3)-H bond functionalization:

N

R2

R2

CHO

R3

H3C

N

R1

R1

R3

TsOH

CH3

+

N

N

Such an activation mechanism was discussed in another publication (Fang-Fang Wang et al.; Org. Biomol. Chem., 10 (2012), 8605-8608):

N

AcOH

ArCHO N

H O Ar

    H AcO

OH

Ar

NH

N

Based on the above literature sources it is possible to predict that (R)-8-(3-amino- piperidin-1-yl)-7-(but-2-ynyl)-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-


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dihydro-purine-2,6-dione containing 4-methyl-quinazolinyl moiety can produce corresponding 1,3-di(4-quinazolinyl)propane derivatives having the following general structure:

O N N

N N

N

O

in which R = H, Alkyl, Aryl

1,3-di(4-quinazolinyl)propane derivatives may be obtained during the preparation of compound I. In order to avoid the presence of the above derivatives it is suggested to use organi...