Efficient asymmetric synthesis of N-[(1R)-6-chloro-2,3,4,9-tetrahydro-1H- carbazol-1-yl]-2-pyridinecarboxamide for treatment of human papillomavirus infections

Organic Process Research and Development

Volumn 11, Issue 3, 2007, Pages 539-545

  Boggs, Sharon D ^a   Cobb, Jeremy D ^a   Gudmundsson, Kristjan S ^a   Jones, Lynda A ^a   Matsuoka, Richard T ^a   Millar, Alan ^a   Patterson, Daniel E ^a   Samano, Vicente ^a   Trone, Mark D ^a   Xie, Shiping ^a   Zhou, Xiao Ming ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 39049118455     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op060223v     Document Type: Article

References (35)

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22. Racemic amine 2 was resolved on a Berger analytical SFC with an HP1100 diode array detector. The sample was monitored at 230 nm under the following conditions: 10% methanol, 10% chloroform, 0.5% trifluoroacetic acid in carbon dioxide with a flow rate of 2 mL/min at 1500 psi, 27 °C on a Daicel AD-H column (3 cm x 25 cm). When the separated enantiomers were run on an analytical column Daicel AD-H (4.6 mm x 250 mm) in 10% methanol, 10% chloroform, 0.5% trifluoroacetic acid in carbon dioxide with a flow rate of 2 mL/min at 1500 psi, 27 °C, the R-isomer had a retention time of 5.57 min, and the S-isomer a retention time of 8.13 min.
23. 2-NH); flow rate: 1 mL/min; detection: 230 nm; temperature: 25 °C; retention time: 28 min for (S)-2, 12.3 min for enantiomer (R)-2. The salt form (13) was analyzed the same way as for free amine 2 after neutralization with aqueous NaOH and extraction into THF.
24. Racemic final product 1 was resolved on a Berger analytical SFC with an HP1100 diode array detector. The sample was monitored at 230 nm under the following conditions: 30% methanol in carbon dioxide with a total flow rate of 2 mL/min at 1500 psi, 40 °C on a Daicel AS-H column (4.6 mm x 250 mm), to give the R-isomer (retention time 5.08 min) and the S-isomer (retention time 7.45 min).
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29. 2O (0.05% TFA), mobile phase B: MeCN (0.05% TFA); gradient: 0-95% B over 8 min; detection: 220 nm; temperature: 40 °C; retention time: 4.45 min for 12a and 4.55 min for its diastereomer; 4.38 min for 12b and 4.49 min for its diastereomer; 4.21 min for 12c and 4.32 min for its diastereomer.
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35. 2NH); flow rate: 1 mL/min; detection: 230 nm; temperature: 25 °C; retention time: 9.3 min for enantiomer (S)-1, 11.2 min for enantiomer (R)-1.