Structure of 330792-70-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 330792-70-6 |
Formula : | C16H12N4O |
M.W : | 276.29 |
SMILES Code : | N#CC1=C(N)NN=C1C2=CC=C(OC3=CC=CC=C3)C=C2 |
MDL No. : | MFCD20270361 |
InChI Key : | HNIMEQCLCNSCGH-UHFFFAOYSA-N |
Pubchem ID : | 22346784 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 21 |
Num. arom. heavy atoms | 17 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 79.66 |
TPSA ? Topological Polar Surface Area: Calculated from |
87.72 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.92 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.33 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.33 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.72 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.63 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.05 |
Solubility | 0.0245 mg/ml ; 0.0000887 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.85 |
Solubility | 0.00391 mg/ml ; 0.0000142 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.74 |
Solubility | 0.000507 mg/ml ; 0.00000184 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.62 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.55 |
* 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 |
---|---|---|
35% | [0427] A mixture of 5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile (1.5 g, 5.4mmol) and K2C03 (2.24 g, 16.3 mmol) in 50 mL of DMF at 80 DC was stirred under N2 for 45min before tert-butyl3-bromo-4-oxopiperidine-1-carboxylate (4.5 g, 16.3 mmol) was added inone portion. Then the mixture was stirred at 80 DC for 1 hr. After cooling down toRT, 150 mLof water and 150 mL of EA was added. Aqueous phase was further extracted with EA (1 00 mL x 3). The combined organic layers were washed with brine, dried over Na2S04 and concentratedto get crude product which was chromatographed on I5 g of silica gel using DCM/MeOH (40011to 20011) as eluant to afford 850 mg (35%) oftert-butyl3-cyano-2-(4-phenoxyphenyl)-5,6-dihydro -4H -pyrazolo[5', I' :2,3 ]imidazo[ 4,5-c ]pyridine-? (8H)-carboxylate as an off-white solid.MS (ESI) m/e [M+ It 455.9. | |
35% | 5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile (1.5 g, 5.4 mmol)And a mixture of K2CO3 (2.24 g, 16.3 mmol) in DMF (50 mL),Stir for 45 minutes under nitrogen at 80C.Then, <strong>[188869-05-8]tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate</strong> (4.5 g, 16.3 mmol) was added in one portion.The reaction mixture was stirred at 80 C for 1 h.It was then cooled to room temperature and water (150 mL) and EA (150 mL) were added.The aqueous phase was further extracted with EA (100 mL x 3) and the combined organic phases were washed with saturated brine, dried over Na2SO4, concentrated, and purified on a tannin extract column (15 g of silica gel, DCM/MeOH = 400/1 to 200/1).An off-white solid product 3-cyano-2-(4-phenoxyphenyl)-5,6-dihydro-4H-pyrazolo[5',1':2,3]imidazo[4, 5-c]tert-Butyl pyridine-7(8H)-carboxylate (850 mg, 35%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With acetic acid; In ethanol; at 20℃; for 16h; | [0565] To a solution of 5-amino-3-(4-phenoxyphenyl)-IH-pyrazole-4-carbonitrile (276 mg, 1.0mmol) in EtOH (10 mL) was added ethyl2-formyl-3-oxopropanoate (144 mg, 1.0 mmol) andHOAc (5 drops). After stirring at RT for 16 hr, the mixture was filtered. The cake was washedwith H20 (10 mL x 2) and dried to afford 250 mg (65percent) of ethyl3-cyano-2-(4-phenoxyphenyl)pyrazolo[l,5-a]pyrimidine-6-carboxylate as a yellow solid. MS (ESI) m/e[M+ It 384.9. |
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