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-[Bis-(6-chloro-2-methyl-pyrimidin-4-yl)-amino]-thiazole-5-carboxylic acid (2-chloro-6-methyl-phenyl)-amide

IP.com Disclosure Number: IPCOM000176077D
Publication Date: 2008-Nov-04
Document File: 4 page(s) / 89K

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The IP.com Prior Art Database

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Page 1 of 4

2-[Bis-(6-chloro-2-methyl-pyrimidin-4-yl)-amino]-thiazole-5-carboxylic acid (2- chloro-6-methyl-phenyl)-amide

     2-[Bis-(6-chloro-2-methyl-pyrimidin-4-yl)-amino]-thiazole-5-carboxylic acid (2- chloro-6-methyl-phenyl)-amide(referred to as "Sub-DAS6") of the following formula:

Cl

 N N

O

Cl

N N

H

 S N

N N Cl

is an impurity formed in the preparation of N-(2-chloro-6-methylphenyl)-2-[[6- chloro-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide ("DAS-6") of formula II;

O

N

Cl

H S N

N

H

N N Cl

II

    which is an intermediate of N-(2-chloro-6-methylphenyl)-2-(6-(4-(3- hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazol-5- carboxamide("DAS")a compound having the following chemical structure:

CH3

CH3

N

N

N

H

Cl O

N

S

N

H

N

N OH

2

Page 2 of 4

    DAS is marketed under the trade name Sprycel ® by Bristol-Myers Squibb Company. Sub-DAS6 is characterized by a ms2 spectrum ion at 520 and Positive ion ESI MS spectrum described in Figure 1.

Figure 1: Positive ion ESI MS spectrum of Sub-DAS6

520

.

1

522.1

100

95

90

85

80

75

70

65

Relative Abundance

60

55

50

45

40

35

524.0

30

25

20

253.2

268.3

270.3

15

10

525.0

526.0

5

225.2

287.3

102.2 192.2

122.3

164.5

304.4 376.2 488.2 516.2

450.3 468.5

328.4

394.2

404.8

527.0

555.9

592.0

0100 150 200 250 300 350 400 450 500 550 600 m/z

Figure 2: Positive ion ESI MS spectrum of Sub-DAS6

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T:

c

ESI

Full

ms2

520.10@35.00

[

140.00 560.00]

100 253.1

268.2

95

90

85

80

75

70

65

Relative Abundance

60

55

50

45

40

35

376.2

30

25

20

15

10

225.1

269.2

5

252.4

377.1 520.2

164.2

191.3

280.0

304.9

335.4

352.3

390.2 461.7

503.1

0100 150 200 250 300 350 400 450 500 550 600 m/z

EXAMPLES

Mass spectrometry
Instrument:
Finnigan LCQ (ion-trap)

Method: ESI, positive ion mode
Conditions: Source Voltage (kV) 3.50, Source Current...