Structure of 4-Chlorofuro[3,2-c]pyridine
CAS No.: 31270-80-1
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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. : | 31270-80-1 |
Formula : | C7H4ClNO |
M.W : | 153.57 |
SMILES Code : | ClC1=NC=CC2=C1C=CO2 |
MDL No. : | MFCD02179768 |
InChI Key : | OPFFYLJLHPZSEO-UHFFFAOYSA-N |
Pubchem ID : | 2779746 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.02 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.03 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.89 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.22 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.48 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.18 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.58 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.86 |
Solubility | 0.214 mg/ml ; 0.00139 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.4 |
Solubility | 0.609 mg/ml ; 0.00397 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.51 |
Solubility | 0.047 mg/ml ; 0.000306 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) |
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 |
-5.66 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 |
1.0 |
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 |
1.0 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) |
2.12 |
* 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 |
---|---|---|
81% | Reference Example 4 4-chlorofuro[3,2-c]pyridine; [Show Image] <strong>[26956-43-4]Furo[3,2-c]pyridin-4(5H)-one</strong> (72.2 g, 534 mmol) was added to phosphorus oxychloride (100 mL) heated to 120C, and the mixture was stirred for 30 min. The solvent was evaporated under reduced pressure. Ice-cooled water was added to the residue, and the mixture was basified with 8M aqueous sodium hydroxide solution and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=30/70) to give the title compound (66.1 g, yield 81%). 1H-NMR (CDCl3) delta: 7.13 (1H, dd, J = 2.2, 1.0 Hz), 7.79 (1H, dd, J = 5.8, 1.0 Hz), 8.27 (1H, d, J = 2.2 Hz), 8.32 (1H, d, J = 5.8 Hz). | |
With trichlorophosphate; at 120℃; for 3h; | 5H-Furo [3,2-c] pyridin-4-one (5.9 g) was suspended with POCI3 (12 ml) and the reaction mixture was stirred for 3 hours at 120 C. After evaporating POCI3, crushed ice was added and poured into the mixture of ethyl acetate and saturated NaHCO3. The corresponding organic phase was separated and dried over NA2SO4 and then concentrated in vacuo. The resultant residue was purified by chromatography on a silica gel column to afford 4-chloro-furo [3,2-c] pyridine (5.6 g) 1 H NMR (400MHZ, DMSO-D6) ppm 8.31 (d, J = 5.8Hz, 1H), 8.26 (d, J = 2.3Hz, 1H), 7.79 (dd, J = 1.0, 5.6 Hz, 1H), 7.13 (dd, J=1.0, 2.3 Hz, 1 H). | |
With trichlorophosphate; In acetonitrile; at 110℃; for 0.0833333h;Microwave irradiation; | General procedure: A solution of 6,7-dimethoxyisoquinolin-1(2H)-one(200 mg, 0.97 mmol), phosphoryl trichloride (0.268 mL, 2.92 mmol) inacetonitrile (5 mL) was stirred at 110 C for 5 minutes under microwaveirradiation. The reaction was quenched with a saturated aqueous sodium bicarbonatesolution and stirred at ambient temperature for 1 h. It was filtered throughcelite and washed with ethyl acetate. The filtrate was concentrated to dryness.The crude material was purified by flash chromatography, eluting with heptanesand ethyl acetate (1:0 to 0:1) to give the desired product as a gum (99 mg,45.4 %). |
With trichlorophosphate; for 3h;Heating / reflux; | [0155] Furopyridone (6,3. 26 g, 24.15 mmol) is treated with phosphorus oxychloride (10 ml) at refluxing temperature for 3 hours. After cooling, the dark solution is poured into ice and basified with aqueous sodium hydroxide to pH-9. The mixture is extracted with chloroform. After evaporation of the chloroform, the brown oil is applied to flash column chromatography on silica gel to give chlorofuropyridine as yellow crystalline solid (7). | |
With trichlorophosphate; at 120 - 140℃; for 2.5h; | Next, Compound (3) (60.0 g, 444 mmol) and phosphorus oxychloride (POCl3) (62 mL, 666 mmol) were added into a reaction bottle. After heating the reaction bottle to 120-140 C. for 2.5 hours, the reaction bottle was cooled to 25 C. The reaction was quenched by water under ice bath. Next, the reaction mixture was neutralized with sodium hydroxide. The mixture was extracted with ethyl acetate (EA) and water. Next, an organic phase was separated and concentrated. Next, after removing water and concentrating, the result was purified by column chromatography. Compound (4) was obtained. The synthesis pathway of the above reaction was as follows: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To the solution of 4-chloro-furo [3, 2-C] PYRIDINE (4.2 g, 0.03 mol) in CCI4 (77 ML) was added BR2 (2.4 ml, 0.046 mol) at 0C and the resultant reaction mixture was stirred for 4 hours at room temperature. The resultant suspension was poured into the mixture of ethyl acetate and 10% Na2SO3. The corresponding organic phase was separated and dried over NA2SO4 and concentrated in vacuo. The crude residue was dissolved in THF (100 ml) and DBU (1, 8-diazabicyclo [5.4. 0] undec-7-ene) (5.6 ml) was added at 0C. The resultant reaction mixture was stirred for 2 hours at room temperature and poured into NAHCO3 and ethyl acetate. The organic layers were separated, dried over anhydrous sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on a silica gel column to afford the titled compound (5.4 g) 1H NMR (400MHZ, CDCI3) PPM 8.32 (d, J = 5.8 Hz, 1 H), 7.72 (s, 1 H), 7.44 (d, J = 5.8 Hz, 1 H), 7.26 (s, 1 H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With sodium hydroxide; bromine; In methanol; tetrachloromethane; | EXAMPLE 543A 3-bromo-4-chlorofuro[3,2-c]pyridine A solution of 4-chlorofuro[3,2-c]pyridine (commercially available, 10.60 g, 69 mmol) in carbon tetrachloride (135 mL) was cooled to -15 C. and bromine (12.13 g, 80 mmol) was added drop-wise over a fifteen minute time period. The mixture was stirred at ambient temperature for eighteen hours. The solvent was removed in vacuo, and the residue was dissolved in methanol (250 mL). A solution of 20% aqueous sodium hydroxide (35 mL) was added and the mixture was stirred 1 hour at ambient temperature. The methanol was removed in vacuo, and the residue was partitioned between water (100 mL) and dichloromethane (50 mL). The combined organic layers were dried over anhydrous magnesium sulfate and the solvent was removed in vacuo to give 3-bromo-4-chloro[3,2-c]pyridine 15.45 g, 96%) as a solid. MS (ESI(+)) m/e 232, 234 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; lithium hydroxide; In 1,4-dioxane; water; at 80℃; for 0.5h;Inert atmosphere; | General procedure: To a solution of 2-chloroheteroaryl compound 1 (0.50 mmol) in 1,4-dioxane (4.0 mL) were added pinacol boronate 3, 5, or 7 (0.60 mmol), Pd(OAc)2 (1.1 mg, 5.0 mumol), S-Phos (4.1 mg, 10.0 mumol), and 2 M LiOH solution (1.0 mL, 2.0 mmol) at room temperature, and the mixture was stirred for 30 min at 80 C under N2 atmosphere. The reaction was quenched by adding water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was removed in vacuo, and the residue was purified by silica-gel column chromatography. The solvent was removed in vacuo, and the residue was triturated with Et2O to give biaryl compounds. |
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