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CAS No. : | 380899-24-1 | MDL No. : | MFCD18251524 |
Formula : | C26H24FN3O3S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZJXIUGNEAIHSBI-IBGZPJMESA-N |
M.W : | 477.55 | Pubchem ID : | 25195495 |
Synonyms : |
GSK649868
|
Num. heavy atoms : | 34 |
Num. arom. heavy atoms : | 20 |
Fraction Csp3 : | 0.27 |
Num. rotatable bonds : | 7 |
Num. H-bond acceptors : | 5.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 133.69 |
TPSA : | 103.68 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | Yes |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -5.52 cm/s |
Log Po/w (iLOGP) : | 3.73 |
Log Po/w (XLOGP3) : | 5.2 |
Log Po/w (WLOGP) : | 5.47 |
Log Po/w (MLOGP) : | 2.87 |
Log Po/w (SILICOS-IT) : | 6.04 |
Consensus Log Po/w : | 4.66 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -6.05 |
Solubility : | 0.000426 mg/ml ; 0.000000891 mol/l |
Class : | Poorly soluble |
Log S (Ali) : | -7.12 |
Solubility : | 0.0000359 mg/ml ; 0.0000000751 mol/l |
Class : | Poorly soluble |
Log S (SILICOS-IT) : | -8.58 |
Solubility : | 0.00000126 mg/ml ; 0.0000000026 mol/l |
Class : | Poorly soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 4.31 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In dichloromethane at 1 - 22℃; | 1 All volumes and weights refer to the weight of Intermediate 12. The reactor was charged with Intermediate 1 1 (1.0 eq) and DMF (0.025 vol, 0.14 eq) in dichloromethane (1.9 vol) at 20 0C. A solution of oxalyl chloride (0.20 vol, 1.0 eq) in dichloromethane (2.1 vol) was added at 20-19 0C over 30 minutes. The mixture was stirred 2 hours at 19-20 0C. Solvent (2.8 vol) was removed at a maximum jacket temperature of 45 0C under reduced pressure. The solution was stored under nitrogen in a feed tank. The reactor was cleaned, dried under vacuum and charged with Intermediate 12 (1.0 eq, 1 wt) and dichloromethane (7.0 vol). Trifluoroacetic acid (3.05 wt, 12 eq) was added at 19-20 0C over 18 minutes. The mixture was stirred overnight at 20-21 0C. The mixture was split in 2 equal portions. Each portion was washed with half saturated aqueous Na2CO3 (8.6 vol) at 20 0C. The combined organic phases were dried over MgSO4 (0.45 wt). After filtration the filtrate was transferred into the cleaned and dried reactor. Dichloromethane (1.3 vol) and triethylamine (0.96 vol, 3eq) were added.The acid chloride solution was added at 1-5 0C over 25 minutes and the mixture was stirred at 19-22 0C overnight. The mixture was split in 2 equal portions. Each portion was washed with saturated aqueous NaHCO3 (7.3 vol) at 20 0C. The combined organic phases were concentrated in the cleaned reactor. The mixture was filtered through a plug of silica gel (0.78 wt) conditioned with ethyl acetate and eluted with ethyl acetate (8.8 vol). The filtrate was concentrated in the cleaned reactor and a solvent change to iPrOAc was performed. The resulting suspension was heated to obtain a clear solution. The solution was cooled and seed crystals (obtained by cooling of about 1 vol% of the clear solution) was added at 57°C. The resulting suspension was concentrated, cooled to 100C, stirred overnight and filtered. The filter cake was washed with iPrOAc and IPA and dried at a max. jacket temperature of 50 0C and reduced pressure at the rotavap to give intermediate grade title compound. Yield (% theory): 48% |