Structure of 7170-01-6
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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. : | 7170-01-6 |
Formula : | C3H5N3 |
M.W : | 83.09 |
SMILES Code : | CC1=NNC=N1 |
MDL No. : | MFCD00233931 |
InChI Key : | PZKFSRWSQOQYNR-UHFFFAOYSA-N |
Pubchem ID : | 305560 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 6 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 21.35 |
TPSA ? Topological Polar Surface Area: Calculated from |
41.57 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.32 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.55 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.11 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.58 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.23 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.63 |
Solubility | 19.7 mg/ml ; 0.237 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.15 |
Solubility | 116.0 mg/ml ; 1.4 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.14 |
Solubility | 6.06 mg/ml ; 0.0729 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 |
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) |
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 |
-7.2 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) |
1.29 |
* 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 |
---|---|---|
49%; 13% | With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; | A mixture of l-fluoro-2-methoxy-4-nitrobenzene (821.414 mg, 4.8 mmol), 5-methyl- lH-l,2,4-triazole (800 mg, 9.63 mmol), K2CO3 (4.8 mmol) and DMSO (8 ml) was stirred at 120 0C for 1 h. After cooling to r.t., the r.m. was poured into ice H2O. The solid was filtered off, washed with H2O and dried in vacuo at 50 0C. Yield: 0.554 g of intermediate 9 (49 percent). The aq. layer was sat. with NaCl, extracted with DCM and the organic layer was dried (MgSO4), filtered and the solvent was evaporated in vacuo. The residue was purified by column chromatography over silicagel (eluent: DCM). The desired fraction was collected and the solvent was evaporated in vacuo. Yield: 0.147 g of intermediate 10 (13 percent). |
49%; 13% | With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; | a) Preparation of intermediate 3 and intermediate 4 (regioisomers) A mixture of l-fluoro-2-methoxy-4-nitrobenzene (821 mg, 4.8 mmol), 5 -methyl- IH- 1,2,4-triazole (800 mg, 9.63 mmol), K2CO3 (4.8 mmol) and DMSO (8 ml) was stirred at 120 0C for 1 h. After cooling, the r.m. was poured into ice water. The solid was filtered off, washed with water and dried in vacuo at 50 0C. Yield: 0.554 g of intermediate 3 (49 percent). The aq. layer was saturated with NaCl, extracted with DCM and the organic layer was dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM). The desired fraction was collected and the solvent was evaporated. Yield: 0.147 g of intermediate 4 (13 percent). |
49%; 13% | With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; | Example A2 a) Preparation of intermediate 3 and intermediate 4A mixture of l-fluoro-2-methoxy-4-nitrobenzene (821 mg, 4.8 mmol), 5-methyl-lH- 1,2,4-triazole (800 mg, 9.63 mmol), K2CO3 (4.8 mmol) and DMSO (8 ml) was stirred at 120 0C for 1 h. After cooling, the r.m. was poured into ice water. The solid was filtered off, washed with H2O and dried (in vacuo; 50 0C). Yield: 0.554 g of intermediate 3 (49 percent). The aq. layer was sat. with NaCl, extracted with DCM and the organic layer was dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM). The desired fraction was collected and the solvent was evaporated. Yield: 0.147 g of intermediate 4 (13 percent). |
49%; 13% | With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; | A mixture of l-fluoro-2-methoxy-4-nitrobenzene (821 mg, 4.80 mmol), 5-methyl-lH- 1,2,4-triazole (800 mg, 9.63 mmol), K2C03 (4.80 mmol) and DMSO (8 ml) was stirred at 120 °C for 1 h. After cooling, the r.m. was poured into ice water. The solid was filtered off, washed with water and dried in vacuo at 50 °C. Yield: 0.55 g ofintermediate 37 (49 percent). The aq. layer was saturated with NaCl, extracted with DCM and the organic layer was dried (MgSC^), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM). The desired fraction was collected and the solvent was evaporated. Yield: 0.15 g ofintermediate 38 (13 percent). |
49%; 13% | With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; | A mixture of l-fluoro-2-methoxy-4-nitrobenzene (821 mg, 4.80 mmol), 5-methyl-lH-1,2,4-triazole (800 mg, 9.63 mmol), K2C03 (4.80 mmol) and DMSO (8 ml) was stirred at 120 °C for 1 h. After cooling, the r.m. was poured into ice water. The solid was filtered off, washed with water and dried in vacuo at 50 °C. Yield: 0.55 g ofintermediate 37 (49 percent). The aq. layer was saturated with NaCl, extracted with DCM and the organic layer was dried (MgS04), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM). The desired fraction was collected and the solvent was evaporated. Yield: 0.15 g of intermediate 38 (13 percent). |
49%; 13% | With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; | A mixture of <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (821 mg, 4.80 mmol), 5-methyl-1H-1,2,4-triazole (800 mg, 9.63 mmol), K2CO3 (4.80 mmol) and DMSO (8 ml) was stirred at 120° C. for 1 h. After cooling, the r.m. was poured into ice water. The solid was filtered off, washed with water and dried in vacuo at 50° C. Yield: 0.55 g of intermediate 37 (49percent). The aq. layer was saturated with NaCl, extracted with DCM and the organic layer was dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM). The desired fraction was collected and the solvent was evaporated. Yield: 0.15 g of intermediate 38 (13percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; | Example 41 b. l-(2-methoxy-4-nitrophenyl)-3-methyl-lH-l,2,4-triazoleA mixture of 3-methyl-lH-[l,2,4]triazole (2.4 g, 29.21 mmol), l-fluoro-2-methoxy-4- nitrobenzene (5.0 g, 29.21 mmol) and potassium carbonate (8.06 g, 58.42 mmol) in DMF (50 mL) was heated overnight at 85°C in a pressure vessel. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was suspended in water and the mixture extracted with dichloromethane. The organic extracts were combined, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was dissolved in dichloromethane (50 mL) and hexane was added in small portions until the solution become slightly turbid. The turbid solution was left at room temperature. The precipitation was collected by filtration, washed with hexane to give 2.5 g of title compound (37 percent Yield).1U NMR (400 MHz, CHLOROFORM-J) delta ppm 2.51 (s, 3 H) 4.10 (s, 3 H) 7.90 - 8.06 (m, 2 H) 8.10 (d, I H) 8.87 (s, I H) |
35% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 85℃; for 16h;Sealed tube; Inert atmosphere; | To a stirred solution of <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (2.5 g, 14.60 mmol) in DMF (25 mL) under an argon atmosphere were added potassium carbonate (4 g, 29.20 mmol) and 3-methyl-1H-1, 2, 4-triazole (1.2 g, 14.60 mmol) at room temperature. The reaction mixture was stirred at 85 oC for 16 h in a sealed tube. After consumption of the starting material (monitored by TLC), the reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2 x 50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography using 15-25percent EtOAc:hexane to afford <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (1.2 g, 35percent) as an off-white solid. 1H-NMR (CDCl3, 400 MHz): delta 8.87 (s, 1H), 8.10 (d, 1H), 8.00-7.97 (m, 2H), 4.10 (s, 3H), 2.50 (s, 3H); LCMS: 234.9 (M+1); (column; Ascentis Express C-18 (50 × 3.0 mm, 2.7 mum); RT 2.02 min. 0.025percent Aq TFA+5percent ACN: ACN+5percent 0.025percent Aq TFA; 1.2 mL/min); TLC: 30percent EtOAc:hexane (Rf: 0.2). |
35% | With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 16h;Inert atmosphere; Sealed tube; | Synthesis of <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (1023) To a stirred solution of <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (2.5 g, 14.60 mmol) in DMF (25 mL) under an argon atmosphere were added potassium carbonate (4 g, 29.20 mmol) and 3-methyl-1H-1,2,4-triazole (1.2 g, 14.60 mmol) at room temperature. The reaction mixture was stirred at 85° C. for 16 h in a sealed tube. After consumption of the starting material (monitored by TLC), the reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography using 15-25percent EtOAc:hexane to afford <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (1.2 g, 35percent) as an off-white solid. 1H-NMR (CDCl3, 400 MHz): delta 8.87 (s, 1H), 8.10 (d, 1H), 8.00-7.97 (m, 2H), 4.10 (s, 3H), 2.50 (s, 3H); LCMS: 234.9 (M+1); (column; Ascentis Express C-18 (50×3.0 mm, 2.7 mum); RT 2.02 min. 0.025percent Aq TFA+5percent ACN: ACN+5percent 0.025percent Aq TFA; 1.2 mL/min); TLC: 30percent EtOAc:hexane (Rf: 0.2). |
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