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Structure of 1186647-69-7
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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. : | 1186647-69-7 |
Formula : | C6H3ClIN3 |
M.W : | 279.47 |
SMILES Code : | ClC1=NC=CC2=C1C(=N[NH]2)I |
MDL No. : | MFCD16877655 |
InChI Key : | PBVPGWHQJRFJQU-UHFFFAOYSA-N |
Pubchem ID : | 53249936 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301-H319 |
Precautionary Statements: | P301+P310-P305+P351+P338 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅲ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 51.62 |
TPSA ? Topological Polar Surface Area: Calculated from |
41.57 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.11 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.13 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.22 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.7 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.18 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.52 |
Solubility | 0.0844 mg/ml ; 0.000302 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.63 |
Solubility | 0.648 mg/ml ; 0.00232 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.1 |
Solubility | 0.0221 mg/ml ; 0.0000791 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 |
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) |
Yes |
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 |
-6.49 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 |
2.0 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) |
2.09 |
* 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 |
---|---|---|
92% | With iodine; potassium hydroxide; In 1,4-dioxane; at 75℃; for 4h; | A solution of <strong>[871836-51-0]4-chloro-1H-pyrazolo[4,3-c]pyridine</strong> (1.5 g, 9.77 mmol, 1.00 equiv), 1,4-dioxane(25 mL), potassium hydroxide (2.0 g, 35.65 mmol, 3.60 equiv), and iodine (4.95 g, 19.50 mmol,2.00 equiv) was stuffed for 4 h at 75 °C. The reaction was quenched by saturated aqueous sodium thiosulfate pentahydrate and the solids were collected by filtration. This resulted in 2.5 g (92percent) of the title compound as a light yellow solid. LC-MS (ES, mlz): 280 [M+H]. |
85% | With N-iodo-succinimide; In N,N-dimethyl-formamide; at 100℃; | To a solution of 4-chloro-lH-pyrazolo[4,3-c]pyridine (5.5 g, 36 mmol) in DMF (50 mL) was added NIS (6.9 g, 69 mmol). The resulted mixture was stirred at 100 °C overnight. Then the mixture was cooled and diluted with water, the precipitate was collected by filtration and dried to to give 4-chloro-3-iodo-lH-pyrazolo[4,3-c]pyridine (8.5 g, 85percent) as a light yellow solid. |
72% | With iodine; potassium hydroxide; In 1,4-dioxane; at 75℃; for 4h; | To a mixture of 4-chloro-1H-pyrazolo [4, 3-c] pyridine (5.8 g, 38 mmol, synthesized according to WO 2010106333A1 and WO 2012038743A1) and KOH (8 g, 142 mmol) in dioxane (100 mL) at room temperature was added iodine (19 g, 76 mmol) . The reaction mixture was stirred at 75 for 4 h and then allowed to cool to room temperature. The solution was diluted with saturated Na2S2O3(aq) and the resulting precipitate was filtered and dried to give a yellow solid (4.1 g) . The filtrate was left standing for 3 days and filtration of the resulting precipitate yielded a further 3.55 g of the product. Combined yield (7.65 g, 72) .1H NMR (400 MHz, CDCl3) delta ppm 7.65 (d, J 6.0 Hz, 1H) , 8.13 (d, J 6.0 Hz, 1H) , 14.22 (s, 1H) . m/z (ESI)+: 280 [M+H]+ |
62% | With N-iodo-succinimide; In N,N-dimethyl-formamide; at 80℃; for 3h; | A solution of <strong>[871836-51-0]4-chloro-1H-pyrazolo[4,3-c]pyridine</strong> (102) (30 mg, 0.196 mmol) and NIS (66 mg 1.5 eq, 0.249mmol) in DMF (1 mL) was heated to 80 °C for 3 h. The mixture was concentrated in vacuo, brine (10 mL) was addedand then extracted with ethyl acetate (3 3 30 mL). The combined organic layer was washed with brine (10 mL), driedover MgSO4 and filtered. The filtrate was concentrated in vacuo to afford the desired product, 4-chloro-3-iodo-1Hpyrazolo[4,3-c]pyridine (103) (34 mg, 62percent yield) as a white solid. ESI-MS m/z : 277.85 [M - H]- .The product obtainedwas used directly in the next step without purification. |
61% | With iodine; potassium hydroxide; In 1,4-dioxane; at 75℃; for 4h; | Intermediate 34-Chloro-3-iodo-1 H-pyrazolo[4, 3-c]pyridiTo a mixture of Intermediate 2 (5.8 g, 38 mmol) and KOH (8 g, 142 mmol) in dioxane (100 ml) at room temperature was added iodine (19 g, 76 mmol). The reaction mixture was stirred at 75 °C for 4 h, and then allowed to cool to room temperature. The solution was diluted with saturated Na2S203 (aq), and the resulting precipitate was filtered and dried to give a yellow solid (4.1 g). The filtrate was left standing for 3 days and filtration of the resulting precipitate yielded a further 2.35 g of the product. Combined yield (6.45 g, 61percent). 1 H NMR (400 MHz, DMSO-d6) delta ppm 7.64 (d, J=6.0 Hz, 1 H), 8.11 (d, J=6.0 Hz, 1 H); m/z (ES+APCI)+: 280 [M + H]+. |
61% | With iodine; potassium hydroxide; In 1,4-dioxane; at 75℃; for 4h; | Intermediate 124-Chloro-3-iodo-1H-pyrazolo[4,3-c]pyridineTo a mixture of Intermediate 11 (5.8 g, 38 mmol) and KOH (8 g, 142 mmol) in dioxane (100 ml) at room temperature was added iodine (19g, 76 mmol). The reaction mixture was stirred at 750C for 4 h, and then allowed to cool to room temperature. The solution was diluted with saturated Na2S2O3 (aq), and the resulting precipitate was filtered and dried to give a yellow solid (4.1 g). The filtrate was left standing for 3 days and filtration of the resulting precipitate yielded a further 2.35 g of the product. Combined yield (6.45 g, 61percent). 1H NMR (400 MHz, DMSO-d6) delta ppm 7.64 (d, J=6.0 Hz, 1 H), 8.11 (d, J=6.0 Hz, 1 H); m/z (ES+APCI)+: 280 [M + H]+. |
6.3 g | With iodine; potassium hydroxide; In 1,2-dimethoxyethane; at 75℃; for 4h; | C) 4-chloro-3-iodo-1H-pyrazolo[4,3-c]pyridine [1033] To a mixture of <strong>[871836-51-0]4-chloro-1H-pyrazolo[4,3-c]pyridine</strong> (4.0 g) and potassium hydroxide (4.4 g) in DME (50 mL) was added iodine (13.3 g) at room temperature. The reaction mixture was stirred at 75°C for 4 hr. The reaction mixture was added to aqueous sodium thiosulfate solution, and the mixture was left stand overnight, and the resulting solid was collected by filtration to give the title compound (6.3 g). MS(ESI+): [M+H]+ 279.9. MS(ESI+), found: 280.1. |
1.57 g | With iodine; potassium hydroxide; In 1,4-dioxane; at 75℃; for 4h; | A solution of 4-chloro-lH-pyrazolo[4,3-c]pyridine (750.0 mg, 4.902 mmol, 1.0 eq), KOH (988.0 mg, 17.647 mmol, 4.0 eq) and 12 (2.49 g, 9.804 mmoL, 2.0 eq) in 1,4- dioxane (20.0 mL) was stirred at 75 °C for 4 h, then cooled and quenched by sat. aq. Na2S03 and the precipitate was collected by filtration to provide 4-chloro-3-iodo-lH- pyrazolo[4,3-c]pyridine (1.57 g). |
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