Structure of 1206977-80-1
*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
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.
4.5
*For Research Use Only !
Change View
Size | Price | VIP Price | US Stock |
Global Stock |
In Stock | ||
{[ item.pr_size ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | Inquiry {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock 1-2 weeks - Inquiry - | Login | - + | Inquiry |
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
1-2weeks
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
CAS No. : | 1206977-80-1 |
Formula : | C6H4ClF2NO |
M.W : | 179.55 |
SMILES Code : | FC(F)OC1=CC=CN=C1Cl |
MDL No. : | MFCD13185847 |
InChI Key : | HPJAGIYYNJKTOR-UHFFFAOYSA-N |
Pubchem ID : | 53302035 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 35.84 |
TPSA ? Topological Polar Surface Area: Calculated from |
22.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.67 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.2 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.18 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.09 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.42 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.61 |
Solubility | 0.44 mg/ml ; 0.00245 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.3 |
Solubility | 0.903 mg/ml ; 0.00503 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.99 |
Solubility | 0.185 mg/ml ; 0.00103 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 |
-5.83 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) |
1.93 |
* 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 |
---|---|---|
72% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 4h; | 0097] As shown in step 3-i of Scheme 3, 2-chloro-3-hydroxypyridine (Compound 1005,2.0 g, 15.4 mmol, obtained from Aldrich Chemical Co.) was dissolved in 40 mL of DMF and5.0 mL of water along with sodium chlorodifluoroacetate (4.71 g, 30.9 mmol, obtained fromLancaster Synthesis, Inc.) and anhydrous potassium carbonate (2.56 g; 18.5 mmol). The reaction mixture was heated in an oil bath at 1000C for 2 hours. Another equivalent of sodium chlorodifluoroacetate and 1.2 equiv. of potassium carbonate were added and heating continued for an additional 2.0 hours. After this time, the reaction was cooled and the volatiles removed under reduced pressure. The residue was partitioned between brine and ethyl acetate and the organics washed once more with brine, dried over Na2SO4, filtered, and the volatiles removed under reduced pressure. The product was purified by silica gel chromatography, eluting with a hexanes/DCM to DCM gradient, to produce 2-chloro-3- (difluoromethoxy)pyridine as a white solid (Compound 1006, 2.0 g, 72% yield): ESMS (M+H) 180; 1H NMR (CDCl3) delta 8.05 (m, IH), 7.45(m, IH), 6.90(m,lH), 6.60(t, IH; J=75Hz), 4.0 l(s, 3H). |
72% | With potassium carbonate; In water; N,N-dimethyl-formamide; at 100℃; for 4h; | As shown in step 3-i of Scheme 3,2-chloro-3-hydroxypyridine (Compound 1005,2.0 g, 15.4 mmol, obtained from Aldrich Chemical Co.) was dissolved in 40 mL of DMF and5.0 mL of water along with sodium chlorodifluoroacetate (4.71 g, 30.9 mmol, obtained fromLancaster Synthesis, Inc.) and anhydrous potassium carbonate (2.56 g; 18.5 mmol). The reaction mixture was heated in an oil bath at 1000C for 2 hours. Another equivalent of sodium chlorodifluoroacetate and 1.2 equiv. of potassium carbonate were added and heating continued for an additional 2.0 hours. After this time, the reaction was cooled and the volatiles removed under reduced pressure. The residue was partitioned between brine and ethyl acetate and the organics washed once more with brine, dried over Na2SO4, filtered, and the volatiles removed under reduced pressure. The product was purified by silica gel chromatography, eluting with a hexanes/DCM to DCM gradient, to produce 2-chloro-3-(difluoromethoxy)pyridine as a white solid (Compound 1006, 2.0 g, 72% yield): ESMS (M+H) 180; 1H NMR (CDCl3) delta 8.05 (m, IH), 7.45(m, IH), 6.90(m,lH), 6.60(t, IH; J=75Hz), 4.0 l(s, 3H). |
72% | With potassium carbonate; In water; N,N-dimethyl-formamide; at 100℃; for 4h; | As shown in step 3(a)-i of Scheme 3(a), 2-chloro-3-hydroxypyridine (Compound 2005, 2.0 g, 15.4 mmol, obtained from Aldrich Chemical Co.) was dissolved in 40 mL of DMF and 5.0 mL of water along with sodium chlorodifluoroacetate (4.71 g, 30.9 mmol, obtained from Lancaster Synthesis, Inc.) and anhydrous potassium carbonate (2.56 g; 18.5 mmol). The reaction mixture was heated in an oil bath at 100C for 2 hours. Another equivalent of sodium chlorodifluoroacetate and 1.2 equiv. of potassium carbonate were added and heating continued for an additional 2.0 hours. After this time, the reaction was cooled and the volatiles removed under reduced pressure. The residue was partitioned between brine and ethyl acetate and the organics washed once more with brine, dried over Na2S04, filtered, and the volatiles removed under reduced pressure. The product was purified by silica gel chromatography, eluting with a hexanes/DCM to DCM gradient, to produce 2-chloro-3- (difluoromethoxy)pyridine as a white solid (Compound 2006, 2.0 g, 72% yield): ESMS (M+H) 180; 1H NMR (CDC13) delta 8.05 (m, 1H), 7.45(m, 1H), 6.90(m,lH), 6.60(t, 1H; J = 75Hz), 4.01(s, 3H). |
69% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 1h; | This reaction was carried out 3 times. A mixture of potassium carbonate (282 g, 2.04 mol) and N,N-dimethylformamide (750 mL) was heated to 100 C and slowly treated, in a drop-wise manner over 1 hour, with a solution of 2-chloropyridin-3-ol (66.7 g, 515 mmol) and sodium chloro(difluoro)acetate (200 g, 1.31 mol) in N,N-dimethylformamide (750 mL). After completion of the addition, the reaction mixture was stirred at 100 C for 1 hour, then cooled to 25 C and partitioned between water (10 L) and tert-butyl methyl ether (5 L). The aqueous layer was extracted with ethyl acetate (4 x 2.5 L), and the combined organic layers were washed with saturated aqueous sodium chloride solution (6 x 2.5 L), dried over sodium sulfate, filtered, and concentrated in vacuo. The combined crude products from the three reactions were purified via distillation at reduced pressure (30-40 C, 1-5 mm Hg) to provide the product as a colorless oil. Yield: 192 g, 1.07 mol, 69%. LCMS m/z 180.0 [M+H]+. 1H NMR (400 MHz, CDCl3) delta 8.26-8.30 (m, 1 H), 7.60 (br d, J=8.2 Hz, 1 H), 7.28 (br dd, J=8.0, 4.8 Hz, 1 H), 6.60 (t, JHF=72.5 Hz, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With sodium; at 100℃; for 6h;Sealed; | [0098] As shown in step 3-ii of Scheme 3, an excess of sodium metal was dissolved into 20 mL anhydrous methanol and <strong>[1206977-80-1]2-chloro-3-(difluoromethoxy)pyridine</strong> (2.O g, 11.1 mmol ) in anhydrous methanol was added. The reaction mixture was stirred in a sealed vessel at 1000C for 6 hours. The volatiles were removed under reduced pressure and the residue was partitioned between EtOAc and brine. The brine was extracted with EtOAc and the combined organics were dried over Na2SO4, filtered, and the volatiles removed under reduced pressure. The product was purified by silica gel chromatography (DCM) to yield 3-(difluoromethoxy)- 2-methoxypyridine as a colorless oil (Compound 1007, 1.1 g, 56% yield: ESMS (M+H) 176. |
56% | With sodium; at 100℃; for 6h;sealed vessel; | As shown in step 3-ii of Scheme 3, an excess of sodium metal was dissolved into 20 mL anhydrous methanol and <strong>[1206977-80-1]2-chloro-3-(difluoromethoxy)pyridine</strong> (2.O g, 11.1 mmol ) in anhydrous methanol was added. The reaction mixture was stirred in a sealed vessel at 1000C for 6 hours. The volatiles were removed under reduced pressure and the residue was partitioned between EtOAc and brine. The brine was extracted with EtOAc and the combined organics were dried over Na2SO4, filtered, and the volatiles removed under reduced pressure. The product was purified by silica gel chromatography (DCM) to yield 3-(difluoromethoxy)- 2-methoxypyridine as a colorless oil (Compound 1007, 1.1 g, 56% yield: ESMS (M+H) 176. |
56% | With sodium; at 100℃; for 6h; | As shown in step 3(a)-ii of Scheme 3(a), an excess of sodium metal was dissolved into 20 mL anhydrous methanol and <strong>[1206977-80-1]2-chloro-3-(difluoromethoxy)pyridine</strong> (2.0 g, 11.1 mmol ) in anhydrous methanol was added. The reaction mixture was stirred in a sealed vessel at 100C for 6 hours. The volatiles were removed under reduced pressure and the residue was partitioned between EtOAc and brine. The brine was extracted with EtOAc and the combined organics were dried over Na2S04, filtered, and the volatiles removed under reduced pressure. The product was purified by silica gel chromatography (DCM) to yield 3-(difluoromethoxy)- 2-methoxypyridine as a colorless oil (Compound 2007, 1.1 g, 56% yield: ESMS (M+H) 176. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With caesium carbonate; In dimethyl sulfoxide; at 80 - 90℃; for 69h; | A suspension of C39 (10 g, 27 mmol), C36 (5.88 g, 32.7 mmol), and cesium carbonate (99%, 13.5 g, 41.0 mmol) in dimethyl sulfoxide (200 mL) was heated to 80 C for 18 hours. Compound C36 (2.9 g, 16 mmol) was added, and the reaction mixture was heated at 90 C for 3 hours, then at 80 C for 66 hours. After cooling to room temperature, the reaction mixture wasdiluted with water and extracted three times with ethyl acetate. The combined organic layers were washed with water (5 x 300 mL), washed with saturated aqueous sodium chloride solution (200 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 25% to 50% ethyl acetate in heptane) provided the product as a viscous, light yellow oil. Yield: 10.8 g, 21.2 mmol, 78%. LCMS m/z 510.2 [M+H]+. 1H NMR (400 MHz, CDCl3) delta 8.05 (dd, J=4.9, 1.7 Hz, 1 H), 7.61-7.65 (m, 1 H), 7.40-7.44 (m, 2H), 7.30-7.36 (m , 2H), 7.24-7.29 (m, 1 H), 7.11-7.16 (m, 2H), 7.10 (dd, J=7.9, 4.9 Hz, 1 H), 7.08 (br d, J=8 Hz, 1 H), 6.70 (t, JHF=73.5 HZ, 1 H), 5.61 (AB quartet, JAB=9.5 Hz, DeltanuAlphaBeta=9.2 Hz, 2H), 4.79 (br s, 2H), 3.04 (s, 3H), 2.16 (br s, 3H), 1.66 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | General procedure: Using an apparatus previously described for method B [21] , potassium hydroxide (2.52 g, 45 mmol, 15 equiv) and water (2.52 g) were added to the reaction vessel and the mixture was allowed to stir until the potassium hydroxide was almost completely dissolved. Then, 2-bromo-3-pyridinol (0.354 g, 3 mmol) was added and the mixture stirred for 30 min, after which acetonitrile (10 mL) was added via syringe and the mixture stirred at room temperature. Fluoroform was then bubbled slowly into the mixture for 2 h, after which the resulting mixture was stirred for one additional hour. After being quenched with water and extracted with ethyl acetate, the ethyl acetate layer was washed with a saturated solution on sodium hydroxide, separated and concentrated. Additional impurities were removed via column chromatography on silica gel using an 80:20 mixture of hexanes/methylene chloride to give a 53% yield of the liquid product, 2-bromo-3-difluoromethoxypyridine (3d): |