Structure of 934758-92-6
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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. : | 934758-92-6 |
Formula : | C3H3ClN2 |
M.W : | 102.52 |
SMILES Code : | ClC1=CC=NN1 |
MDL No. : | MFCD25980930 |
InChI Key : | IJPFBRONCJOTTA-UHFFFAOYSA-N |
Pubchem ID : | 6426710 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 6 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 23.6 |
TPSA ? Topological Polar Surface Area: Calculated from |
28.68 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.8 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.06 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.2 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.91 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.03 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.84 |
Solubility | 1.5 mg/ml ; 0.0146 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.38 |
Solubility | 4.29 mg/ml ; 0.0419 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.78 |
Solubility | 1.72 mg/ml ; 0.0167 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 |
-6.09 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 |
0.0 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) |
1.21 |
* 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 |
---|---|---|
51% | With triethylamine; In acetonitrile; at 60℃; for 4h; | 1 -Benzenesulfonyl-3 -chloropyrazole (VII)A solution of <strong>[934758-92-6]5-chloropyrazole</strong> (35 mg, 0.34 mmol; see Intermediate (VI) above), benzene sulfonylchloride (0.044 mL5 0.34 mmol), and triethylamine (0.047 mL, 0.34 mmol) in acetonitrile (250 mL) was stirred for 4 h at 600C. The mixture was cooled and concentrated. Purification by chromatography (1:4 EtO Ac/heptane) gave the title compound as colourless needles (Yield: 42 mg, 51%). EPO <DP n="47"/>1H-NMR (DMSO-d6): delta 8.61 (d, IH)5 8.01 (d, 2H)5 7.84 (t, IH)5 7.71 (t, 2H)5 7.79 (d, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | 5-Chloropyrazole (VDBuLi (1.6M, 3.4 mL, 5.4 mmol) was added under argon to a solution of1-benzenesulfonylpyrazole (750 mg, 3.6 mmol; see Intermediate (V) above) in THF (50 mL) at -780C. The mixture was stirred for 45 min before hexachloro- ethane (1.70 g, 7.2 mmol) was added in one portion. After stirring at -780C for 10 min, the mixture was allowed to warm to 10- 150C over 75 min. The mixture was poured into H2OZNH4Cl (1:1, aq, sat, 50 mL). The layers were separated and the aqueous phase was extracted with EtOAc (2 x 50 mL). The combined organic phases were dried (Na2SO4) and concentrated. The semi-solid residue was dissolved in MeOH (30 mL) followed by addition of sodium methoxide (30% in MeOH, 1.6 mL, 7.2 mmol). Stirring at it for 45 min, addition Of NaHCO3 (sat., aq., 1 mL) followed by extraction, concentration of the extract and purification of the residue by chromatography (1:1 EtOAc/ heptane) gave the title compound as a white solid (Yield: 78 mg, 21%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; water; at 20 - 45℃; | 5-chloro-lH-pyrazole (50.8 mmol) was dissolved in ethanol (55 mL). A solution of formalin (15.2 g, 508 mmol, 37%) was added at room temperature, and the mixture was heated at 450C overnight. The reaction mixture was evaporated and dried under vacuum, and the residue was triturated in methanol. The solid was filtered and rinsed with methanol. The filtrate was evaporated, and crude (5-chloro-lH-pyrazol-l- yl)methanol was obtained and used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With trifluoroacetic acid; In dichloromethane; at 20℃; for 2h; | 5-Chloro-lH-pyrazole.[0500] To a solution of 5-chloro-N,N-dimethyl-lH-pyrazole-l-sulfonamide (30 g, 143 mmol) in dichloromethane (500 mL) was added trifluoroacetic acid (45.7 g, 401 mmol). The reaction mixture was stirred for 2 h at room temperature and quenched by water. The pH of the solution was adjusted to 8 with saturated sodium bicarbonate. The resulting solution was extracted with dichloromethane and concentrated in vacuo to afford 5-chloro-lH-pyrazole as a reddish solid (14 g , 95%). LCMS (ESI): M+H+ = 103.0. |
With trifluoroacetic acid; In dichloromethane; at 0 - 20℃; for 48h; | 5-chloro-N,N-dimethyl-lH-pyrazole-l -sulfonamide (8.9 g, 50.8 mmol) was dissolved in anhydrous dichloromethane (40 mL), TFA (80 mL, 1016 mmol) was added at 00C, and the mixture was stirred at room temperature for 2 days. The mixture was partially evaporated, hexane was added, and the solid was filtered and then rinsed with hexane. The filtrate was evaporated, and the crude 5-chloro-lH-pyrazole was used in the next step without further purification |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.2% | With nitric acid; acetic anhydride; acetic acid; at 0 - 20℃; | Fuming nitric acid (14.00 ml, 329 mmol) was added at 0 C over a period of 10 min to a solution of <strong>[934758-92-6]5-chloro-1H-pyrazole</strong> (10.0 g, 97.5 mmol) in acetic acid (14.0 ml, 245 mmol). The resulting mixture was stirred at 0 C for 2 h, then acetic anhydride (33.0 ml, 349 mmol) was added and the reaction mixture was stirred at rt. Progress of the reaction was monitored by TLC and LCMS and when starting material was deemed completely consumed (after 4h), the reaction mixture was poured into ice-water (70 mL) and basified with Na2C03 (60 g) and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with aqueous saturated sodium bicarbonate (100 mL) and brine (50 mL), dried over Na2S04 and concentrated. The afforded solid was washed with n-pentane which gave the title compound (7.0 g, 6.2%) as a solid. MS (ES+) 147.93 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With nitric acid; acetic anhydride; acetic acid; at 20℃; | To a solution of 5-chloro-lH-pyrazole (14 g, 136 mmol) in acetic acid/acetic anhydride (36 ml .792 ml . ) was added fuming nitric acid (36 mL). The resulting solution was stirred overnight at room temperature, and then diluted with water (500 mL). The solids were collected by filtration to afford 5- chloro-1 -nitro- lH-pyrazole as a yellow solid (7 g, 35%). |
6.2% | Fuming nitric acid (14.00 ml, 329 mmol) was added at 0 'C over a period of 10 min to a solution of 5-chloro-1 H-pyrazole (10.0 g, 97.5 mmol) in acetic acid (14.0 ml, 245 mmol). The resulting mixture was stirred at 0 'C for 2 h, then acetic anhydride (33.0 ml, 349 mmol) was added and the reaction mixture was stirred at rt. Progress of the reaction was monitored by TLC and LCMS and when starting material was deemed completely consumed (after 4h), the reaction mixture was poured into ice-water (70 mL) and basified with Na2C03 (60 g) and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with aqueous saturated sodium bicarbonate (100 mL) and brine (50 mL), dried over Na2S04 and concentrated. The afforded solid was washed with n-pentane which gave the title compound (7.0 g, 6.2%) as a solid. MS (ES+) 147.93 [M+H]+. | |
To a soution of 5-choro-1H-pyrazoe (3.88 g, 35.2 mmoD in AcOH (5.10 m, 89 mmoD was added at 0C dropwise 90% aqueous HNO3 (5.10 m, 35.2 mmo) and the reaction mixture was stirred at 0C for 2h. Ac20 (12.92 mL 137 mmo) was then added dropwise. The mixture was stirred at RT for 4h, The mixture was poured nto ce-water and AcOEt and Na2003 (33.6 g, 317 mmo) were added. The organic phase was separated and the aqueous phase was extracted with AcOEt, The combined organic ayers were washed with aqueous saturated NaHCO3 and brine, dried over Na2SO4 and concentrated to afford 5-choro-1-nitro-1H-pyrazoe. M/z = 146/148 [M-Hj-. Rt = 0.71 mm (UPLC Method E32), 1H NMR (400 MHz, DMSO-d6): 6 ppm: 8.91 (d, IH), 6.90 (d, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; copper(l) chloride; isopentyl nitrite; In water; acetonitrile; at 0 - 20℃; for 180h;Inert atmosphere; | To a souUon of 1H-pyrazo-5-amne (23.6 g, 284 mmo) n CH3CN (1 L) under a nitrogen atmosphere were added HC (140 m, 1420 mmo, 32%) and copper chorde (56.3 g, 568 mmo) at 0C, sopenty ntrte (80 mL 568 mmo) was added at 0C and the mixture was stirred at 0C for 2 days. sopenty nitrite (20 m, 0.5 eq) was added and the mixture was stirred at RT for another 5.5 days. The reaction mixture was sowy poured into ammonium hydroxide (1 L, 25%) and extracted with AcOEt. The organic phase was separated and the aqueous phase was extracted with AcOEt. The combined organic ayers were washed with brine, dried over Na2SO4 and concentrated. The crude product was purified by sWca ge co?umn chromatography (hexane / TBME from 1:0 to 4:6) to afford 5-choro-1H-pyrazoe. Mz = 103/105 [M+H]+, Rt = 0.48 mm (UPLC Method B2), 1H NMR (600 MHz, DMSO-d6) : 6 ppm: 1300 (bs, IH), 7.79 (t, IH), 6.29 (t, IH), isoarny acoho :4.28 (t, IH), 3.41 (q, 2H), 1.30 (q, 2H), 0.85 (d, 6H). |
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