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SOLID STATE FORMS OF TOFACITINIB INTERMEDIATE

IP.com Disclosure Number: IPCOM000235929D
Publication Date: 2014-Mar-31
Document File: 3 page(s) / 44K

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SOLID STATE FORMS OF TOFACITINIB INTERMEDIATE

(3R,4R)-(1-Benzyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine of the following chemical structure:

N

  N N

N NH

is an intermediate in the preparation of (3R,4R)-4-methyl-3-(methyl-7H-pyrrolo [2,3-d]pyrimidin-4- ylamino)-N-oxo-1-piperidinepropanenitrile, 2-hydroxy-1,2,3-propanetricarboxylate (1:1), known as Tofacitinib citrate.

Provided are processes for the preparation of solid state forms the (3R,4R)-(1-Benzyl-4-methyl- piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine.

Example 1

(3R,4R)-(1-Benzyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine was diluted in 4 vol of methanol and the resulting solution was added slowly above 20 vol of water at 2 ºC. The resulting suspension was stirred 1 h and it was filtered, washed twice with 1 vol of water and dried at 40 ºC until constant weight was achieved. Powder XRD analysis gave the diffractogram shown in figure 1.

counts

0

5

10

15

20

25

30

35

40

45

50

2-theta (º)

Figure 1: Powder XRD diffractogram for (3R,4R)-(1-Benzyl-4-methyl-piperidin-3-yl)-methyl-(7H- pyrrolo[2,3-d]pyrimidin-4-yl)-amine in example 1.


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Example 2 (process according to U.S. patent No. 7,301,023, Example 6)

2.285 g of (3R,4R)-(1-Benzyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine were dissolved in 5 vol. of isopropyl acetate (11.4 mL) at ambient temperature. Then 5 vol. of hexanes
(11.4 mL) were added and the resulting...