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Process for preparing of 8-Bromo-7-(but-2-yn-1-yl)-3-methyl-1- ((4-methylquinazolin-2-yl)methyl)-3,7-dihydro-1H-purine-2,6- dione and crystalline form thereof

IP.com Disclosure Number: IPCOM000239662D
Publication Date: 2014-Nov-23
Document File: 2 page(s) / 83K

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Process for preparing of 8-Bromo-7-(but-2-yn-1-yl)-3-methyl-1- ((4-methylquinazolin-2-yl)methyl)-3,7-dihydro-1H-purine-2,6- dione and crystalline form thereof

Disclosed herein after is a process for preparation of 8-Bromo-7-(but-2-yn-1-yl)-3- methyl-1-((4-methylquinazolin-2-yl)methyl)-3,7-dihydro-1H-purine-2,6-dione (referred herein as compound I) having the following chemical structure:

O N N

Compound I is an intermediate in a process for preparing 8-[3(R)-Aminopiperidin-1-yl]- 7-(2-butynyl)-3-methyl-1-(4-methylquinazolin-2-ylmethyl)xanthine.

Figure 1: crystalline form of compound I

Main XRD peaks of the crystalline form of compound I are: 9.7, 11.7, 12.0, 12.7, 13.8,
14.4, 16.0, 17.0, 17.5, 18.1, 19.4, 19.9, 20.4, 20.8, 21.4, 22.6, 22.9, 23.3, 24.0, 24.5,
26.0, 26.8, 27.4, 28.3, 28.9, 29.7, 30.2, 31.6, 32.1, 32.6, 33.1, 33.6, 35.0, 36.2, 37.0 and
38.4 ± 0.2 degrees 2-theta.

The analysis was performed on ARL (SCINTAG) powder X-Ray diffractometer model X'TRA equipped with a solid state detector. Copper radiation of 1.5418 Å was

N N

Br

N O N


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used. Scanning parameters: range: 2-40 degrees two-theta; scan mode: continuous scan; step size: 0.05°.; and a rate of 3 deg/min.

Expample 1: Preparation of a crystalline form of compound I:

N

N Cl

O

N

O

N

N

HN

N N

N

Br

Br

O

O N

N N

3-Methyl-7-(2-butyn-1-yl)-8-bromoxanthine was mixed with equimolar amount of 2- (chloromethyl)-4-methylquinazoline in N-methylpyrrolidone and toluene in the presence of potassium carb...