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Impurities of (1S, 2S, 3R, 5S)-3-[7-[[(1R,2S)-2-(3,4- difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3- triazolo[4,5,d]pyrimidine-3-yl]-5-(2-hydroxyethoxy)- 1,2-cyclopentanediol

IP.com Disclosure Number: IPCOM000234711D
Publication Date: 2014-Jan-30

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The IP.com Prior Art Database

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   Impurities of (1S, 2S, 3R, 5S)-3-[7-[[(1R,2S)-2-(3,4- difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3- triazolo[4,5,d]pyrimidine-3-yl]-5-(2-hydroxyethoxy)- 1,2-cyclopentanediol

    (1S, 2S, 3R, 5S)-3-[7-[[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino]-5- (propylthio)-3H-1,2,3-triazolo[4,5,d]pyrimidine-3-yl]-5-(2-hydroxyethoxy)- 1,2- cyclopentanediol referred herein as Compound X, has the following chemical structure:

 


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Provided herein are impurities of Compound X and processes for their preparation.

 


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F

F

F

S

O

 N N

N

S

N N

N

N N

N N

   O OH

HO

  N N

HO F

N

   N S

N

OH

HO

O

  OH OH

N N

OH

O

     OH HO

N

O

O

   N N

S

Compond-20

Compond-19

Cl

S

O

HO

 N N

N

N

 N N

O

N N S

N N

Cl

N N S

O

N

   O OH

HO

  N N

HO

  N N

OH

N

OH

N

   N S

HO

HO

O

OH

OH

Compond-21

O

Compond-22

S

N N

N

N N

F

F

HO

O

  OH OH

S

O

 N N

N N

O

N

O

     OH HO

N

O

N N

   N N

S

   OH OH

HO

Compond-23

Compond-24

2-(((1S,2S,3S,4R)-4-(7-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)-5- (propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,3-dihydroxycyclopentyl)oxy)ethyl

 


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acetate (Compound-1). 1H NMR (400 MHz, DMSO-d6: δ 9.37 (s, 1H), 7.34-7.32 (m, 3H), 5.17-4.95 (m, 3H), 4.59-4.54(m, 1H), 4.15-4.13 (m, 2H), 3.95(brs, 1H), 3.79(brs, 1H), 3.73-3.66 (m, 2H), 3.17-3.09 (m, 1H), 2.99-2.85 (m, 2H), 2.67-2.62(m, 1H), 2.14-2.01(m, 2H), 2.04(s, 3H), 1.70-1.38 (m, 4H), 0.83 (t, J = 8Hz, 3H); LC-MS: [M+H]+ = 565

2-(((1S,2S,3S,4R)-4-(7-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)-5- (propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,3-dihydroxycyclopentyl)oxy)ethyl formate (Compound-2). 1H NMR (400 MHz, DMSO-d6: δ 9.38-8.95 (m, 1H), 8.26 (s, 1H), 7.37-7.23 (m, 2H), 7.08 (brs, 1H), 5.17(d, J = 4Hz, 1H), 5.11(d, J = 4Hz, 1H), 5.01(q, J = 8Hz, 1H), 4.59-4.54(m, 1H), 4.26-4.24 (m, 2H), 3.96(brs, 1H), 3.81-3.54(m, 3H), 3.18-3.10(m, 1H), 2.99-2.82 (m, 2H), 2.70-2.55 (m, 1H), 2.13-2.02(m, 2H), 1.72-1.36(m, 5H), 0.83 (t, J = 8Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ 169.66,1.62, 154.43, 149.84,139.75,123.66,123.32,123.29,117.57,117.41,115.40,115.22,82.29,74.73,74.18,67.23,63.37,61.02,3


4.54,33.46,32.79,24.50,22.77,15.46,13.42LC-MS: [M+H]+ = 551

N-(3-((1R,2S,3S,4S)-2,3-dihydroxy-4-(2-hydroxyethoxy)cyclopentyl)-5-(propylthio)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-7-yl)acetamide (Compound-3); LC-MS: [M+H]+ = 413

N-(3-((1R,2S,3S,4S)-2,3-dihydroxy-4-(2-hydroxyethoxy)cyclopentyl)-5-(propylthio)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-7-yl)formamide (Compound-4); LC-MS: [M+H]+ = 399

(1S,2S,3R,5S)-3-(7-(((1R,2S)-2-(2-fluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol (Compound-5);

1H NMR (400 MHz, DMSO-d6: δ 9.39-8.9 (m, 1H), 7.23-7.14 (m, 4H), 5.13 (d, J = 8Hz, 1H),


5.05 (d, J = 4Hz, 1H), 4.95 (q, J = 8Hz, 1H), 4.63-4.52(m, 2H), 3.94 (brs, 1H), 3.75(brs, 1H),


3.49-3.40(m, 3H), 3.10-2.83(m, 2H), 2.67-2.63(m, 1H), 2.35-2.22(m, 1H), 2.07-1.98(m, 1H),


1.71-0.98(m, 5H), 0.79 (t, J = 8Hz, 3H...