Structure of 42098-25-9
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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. : | 42098-25-9 |
Formula : | C4H4ClN3O2 |
M.W : | 161.55 |
SMILES Code : | O=[N+](C1=C(Cl)N(C)N=C1)[O-] |
MDL No. : | MFCD21607270 |
InChI Key : | POXLZEWCWNUVDW-UHFFFAOYSA-N |
Pubchem ID : | 12344836 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 37.32 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.64 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.12 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.02 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.98 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.33 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.97 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.49 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.79 |
Solubility | 2.63 mg/ml ; 0.0163 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.95 |
Solubility | 1.83 mg/ml ; 0.0113 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.78 |
Solubility | 26.6 mg/ml ; 0.164 mol/l |
Class? Solubility class: Log S scale |
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 |
Yes |
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) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.56 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 |
2.0 |
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 |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.87 |
* 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 |
---|---|---|
83% | With diisopropylethylamine; In ethanol; at 130℃; for 1h;Microwave irradiation; | Example 56 3,3-Difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidine A mixture of 5-chloro-1-methyl-4-nitro-1H-pyrazole (0.1 g, 4.5 mmol), <strong>[496807-97-7]3,3-difluoropiperidine hydrochloride</strong> (0.14 g, 0.93 mmol) and DIPEA (0.5 mL, 2.8 mmol) in EtOH (3 mL) was heated at 130 C. in a microwave for 1 hr. Additional DIPEA (0.5 mL, 2.8 mmol) and <strong>[496807-97-7]3,3-difluoropiperidine hydrochloride</strong> (0.29 g, 1.8 mmol) were added and the mixture was heated at 130 C. in a microwave for 2 hr. The solvent was removed under reduced pressure and the crude product was purified via silica gel column chromatography (0-60% EtOAc/isohexane) to yield 3,3-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidine as a yellow oil (127 mg, 83%). 1H NMR (400 MHz, CDCl3) delta 8.04 (s, 1H), 3.80 (s, 3H), 3.41-3.29 (m, 2H), 3.26-3.04 (m, 2H), 2.17-2.03 (m, 2H), 1.97-1.88 (m, 2H). |
83% | With N-ethyl-N,N-diisopropylamine; In ethanol; at 130℃; for 3h;Microwave irradiation; | Example 56 3,3-Difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidine A mixture of 5-chloro-1-methyl-4-nitro-1H-pyrazole from Example 1 (0.1 g, 4.5 mmol), <strong>[496807-97-7]3,3-difluoropiperidine hydrochloride</strong> (0.14 g, 0.93 mmol) and DIPEA (0.5 mL, 2.8 mmol) in EtOH (3 mL) was heated at 130 C. in a microwave for 1 hr. Additional DIPEA (0.5 mL, 2.8 mmol) and <strong>[496807-97-7]3,3-difluoropiperidine hydrochloride</strong> (0.29 g, 1.8 mmol) were added and the mixture was heated at 130 C. in a microwave for 2 hr. The solvent was removed under reduced pressure and the crude product was purified via silica gel column chromatography (0-60% EtOAc/isohexane) to yield 3,3-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidine as a yellow oil (127 mg, 83%). 1H NMR (400 MHz, CDCl3) delta 8.04 (s, 1H), 3.80 (s, 3H), 3.41-3.29 (m, 2H), 3.26-3.04 (m, 2H), 2.17-2.03 (m, 2H), 1.97-1.88 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With N-ethyl-N,N-diisopropylamine; In ethanol; at 140℃; for 5h; | Step A. (+-)-1-(1-Methyl-4-nitro-1H-pyrazol-5-yl)-3-(trifluoromethyl)piperazine A mixture of (+-)-<strong>[131922-05-9]2-(trifluoromethyl)piperazine</strong> (1 g, 6.2 mmol), 5-chloro-1-methyl-4-nitro-1H-pyrazole (2.1 g, 13 mmol), DIPEA (2.4 g, 18.6 mmol) in EtOH (10 mL) was heated in a microwave oven at 140 C. for 5 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel chromatography using DCM/MeOH (10:1) as eluting solvents to afford (+-)-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)-3-(trifluoromethyl)piperazine as a yellow oil (1.8 g, 99%). MS (ESI) m/z: 280 [M+H+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.7% | With potassium carbonate; In dimethyl sulfoxide; at 75℃; for 3h;Inert atmosphere; | Potassium carbonate (15.40 g, 111.42 mmol) was added in one portion to a stirred, RT solution of 5-chloro-l-methyl-4-nitro-pyrazole (6.0 g, 37.140 mmol) and tert-butyl methyl melonate (8.74 g, 50.139 mmol) in anhydrous DMSO (100 mL) under nitrogen. The mixture was heated at 75 °C for 3 hours before being cooled and allowed to stand at RT overnight. The mixture was poured into water (500 mL), acidified with 2N HC1 (80ml, PH 5) and extracted with EtOAc (2 x 250 mL, 2x200ml). The combined organics were dried (MgS04) and the solvent removed under reduced pressure. The residue was purified via silica gel chromatography (0 - 30percent EtOAc/heptane) to afford 1-tert-butyl 3-methyl 2-(l-methyl-4- nitro-lH-pyrazol-5-yl)malonate as a colorless solid (10.3g, 92.7percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tris-(dibenzylideneacetone)dipalladium(0); potassium fluoride dihydrate; tri tert-butylphosphoniumtetrafluoroborate; In tetrahydrofuran; at 85℃; for 2h;Inert atmosphere; Microwave irradiation; | A mixture of 5-chloro- l-methyl-4-nitro- lH-pyrazole (200 mg, 1.25 mmol), potassium fluoride dihydrate (235 mg, 2.5 mmol) and <strong>[1025707-93-0]3,4-dihydro-2H-pyran-6-boronic acid pinacol ester</strong> (394 mg, 1.88 mmol) in THF (3 mL) was degassed by bubbling nitrogen through it for 15 min. Tris(dibenzylideneacetone)dipalladium/tri-tert-butyl phosphonium tetrafluoroborate mixture (mole ratio: 1/1.2, 151 mg, 0.13 mmol) was added and the mixture degassed for a further 10 min before being heated in the microwave at 85 C for 2 hr. Water (10 mL) was added and the mixture extracted with EtOAc (3 x 5 mL). The combined organic layers were passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel chromatography (0-5% EtOAc/isohexane) gave 5-(3,4- dihydro-2H-pyran-6-yl)- l-methyl-4-nitro- lH-pyrazole as a yellow solid (215 mg, 82%). NMR (400 MHz, CDC13) delta 8.04 (s, 1H), 5.22 (t, J = 3.9 Hz, 1H), 4.20 (t, J = 5.1 Hz, 2H), 3.88 (s, 3H), 2.31-2.24 (m, 2H), 2.05- 1.96 (m, 2H). |
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