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Crystalline forms of 4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}benzoic acid Disclosure Number: IPCOM000240821D
Publication Date: 2015-Mar-05
Document File: 2 page(s) / 121K

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Crystalline forms of 4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}benzoic acid Provided are processes for the preparation of solid state forms of 4-methyl-3-{[4-(pyridin-3- yl)pyrimidin-2-yl]amino}benzoic acid (compound 1).

Example 1

In a 250 mL reactor were charged methyl-3-guanidino-4-methylbenzoate nitrate, 3- (dimethylamino)-1-(pyridine-3-yl)prop-2-en-1-one, NaOH pellets and n-butanol. The mixture was heated to reflux under N2 for about 36 hours and then cooled to 80ºC. NaOH aqueous solution was added and the mixture was refluxed for another 1h and cooled to 45ºC.

HCl aqueous solution was added to the reaction to adjust the pH value to 4-5. The mixture was cooled to 25°C, stirred overnight, filtered and washed with water and isopropyl ether. The product was dried over vacuum at 60°C for 16 hours (purity: >99%, yield: 88.2%).

The product of example 1 was analyzed by XRPD to give pattern according to figure 1.

Figure 1

Example 2

In a 100 mL reactor were charged Methyl-3-guanidino-4-methylbenzoate nitrate, 3- (dimethylamino)-1-(pyridine-3-yl)prop-2-en-1-one, NaOH pellets, TBAB and toluene. The

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mixture was heated at 100ºC under N2 for about 12 hours and then cooled to 60ºC. 30% NaOH solution, ethanol and water were charged and the reaction mixture was stirred at 60°C for 3 h.

HCl conc. was added to the mixture at 60°C until pH value of 7.5-8 and stirred for 1 hour at this pH. The pH value was adjusted to 4-5, cooled down to 20 ºC in 2h...