Structure of 724788-64-1
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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. : | 724788-64-1 |
Formula : | C12H11BrN2O3 |
M.W : | 311.13 |
SMILES Code : | CCOC(=O)C1=CN=C2C=CC(OC)=NC2=C1Br |
MDL No. : | MFCD20921954 |
InChI Key : | KXIRJHCVVKYTLS-UHFFFAOYSA-N |
Pubchem ID : | 68454651 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 69.82 |
TPSA ? Topological Polar Surface Area: Calculated from |
61.31 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.28 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.42 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.58 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.85 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.82 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.39 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.44 |
Solubility | 0.113 mg/ml ; 0.000362 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.35 |
Solubility | 0.139 mg/ml ; 0.000447 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.77 |
Solubility | 0.00525 mg/ml ; 0.0000169 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) |
Yes |
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 |
-6.48 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 |
0.0 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) |
2.31 |
* 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 |
---|---|---|
90% | With phosphorus tribromide; In N,N-dimethyl-formamide; at 20℃; for 0.75h; | A suspension of 6-methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester (74.57 g, 300 mmol) in dry DMF (260 mL) under argon was stirred efficiently* in a water bath (to maintain approximately room temperature - may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 mL, 316 mmol) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.56 g, 90%). |
90% | With phosphorus tribromide; In N,N-dimethyl-formamide; at 20℃; for 0.75h; | c) 4-Bromo-6-methoxy-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester; A suspension of 6-methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester (74.57 g, 300 mmole) in dry DMF (260 ml_) under argon was stirred efficiently* EPO <DP n="23"/>in a water bath (to maintain approximately RT - may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 mL, 316 mmole) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.56 g, 90%). |
90% | With phosphorus tribromide; In N,N-dimethyl-formamide; at 20℃; for 0.75h; | A suspension of 6-methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester (74.57 g, 300 mmol) in dry DMF (260 mL) under argon was stirred efficiently* in a water bath (to maintain approximately room temperature - may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 mL, 316 mmol) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.56 g, 90%). |
90% | (c) 4-Bromo-6-methoxy-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester; A suspension of 6-methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxylic acid . ethyl ester (74.57 g, 300 mmol) in dry DMF (260 mL) under argon was stirred efficiently* in a water bath (to maintain approximately room temperature - may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 mL, 316 mmol) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.56 g, 90%). | |
90% | With phosphorus tribromide; In N,N-dimethyl-formamide; at 20℃; for 0.75h; | A suspension of 6-methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester (74.57 g, 300 mmole) in dry DMF (260 mL) under argon was stirred efficiently* in a water bath (to maintain approximately RT - may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 mL, 316 mmole) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.56 g, 90%). |
90% | c) 4-Bromo-6-methoxy-[1.5]naphthyridine-3-carboxylic acid ethyl ester; A suspension of <strong>[53241-92-2]6-methoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid ethyl ester</strong> (74.57 g, 300 mmole) in dry DMF (260 mL) under argon was stirred efficiently* in a water bath (to maintain approximately RT-may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 mL, 316 mmole) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.56 g, 90%). | |
90% | c) 4-Bromo-6-methoxy-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester; A suspension of 6-methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester (74.57 g, 300 mmole) in dry DMF (260 mL) under argon was stirred efficiently* in a water bath (to maintain approximately RT - may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 mL, 316 mmole) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.56 g, 90%). | |
90% | (c) 4-Bromo-6-methoxy-[1,5]naphthyridine-3-carboxylic acid ethyl ester; A suspension of 6-methoxy-4~oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acidethyl ester (74.57 g, 300 mmol) in dry DMF (260 ml) under argon was stirred efficiently* ina water bath (to maintain approximately room temperature - may need slight ice-coolingon a large scale). Phosphorus tribromide (30.0 mL, 316 mmol) was added dropwise over15 min and stirring was continued for an additional 30 min. Water (1 L) was added,followed by saturated sodium carbonate solution to pH 7. The solid was collected bysuction filtration, washed with water and dried under vacuum over phosphorus pentoxideto give the title compound (83.56 g, 90%).; c) 4-Bromo-6-methoxy-[1,5]naphthyridine-3-carboxylic acid ethyl ester; A suspension of 6-methoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acidethyl ester (74.57 g, 300 mmole) in dry DMF (260 ml_) under argon was stirred efficiently*in a water bath (to maintain approximately RT - may need slight ice-cooling on a largescale). Phosphorus tribromide (30.0 ml_, 316 mmole) was added dropwise over 15 minand stirring was continued for an additional 30 min. Water (1 L) was added, followed bysaturated sodium carbonate solution to pH 7. The solid was collected by suction filtration,washed with water and dried under vacuum over phosphorus pentoxide to give the titlecompound (83.56 g, 90%). | |
90% | With phosphorus tribromide; In N,N-dimethyl-formamide; at 20℃; for 0.75h; | c) 4-Bromo-6-methoxy-[1 ,5]naphthyridine-3-carboxylic acid ethyl esterA suspension of 6-methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester (74.57 g, 300 mmole) in dry DMF (260 mL) under argon was stirred efficiently* in a water bath (to maintain approximately RT - may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 mL, 316 mmole) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.56 g, 90%). |
90% | With phosphorus tribromide; In N,N-dimethyl-formamide; for 0.75h;Product distribution / selectivity; | A suspension of 6-methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxyIic acid ethyl ester (74.57 g, 300 mmole) in dry DMF (260 mL) under argon was stirred efficiently* in a water bath (to maintain approximately RT - may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 mL, 316 mmole) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.56 g, 90%). c. 4-bromo-6-methoxy-[1,5]naphthyridine-3-carboxylic acid ethyl ester A suspension of 6-methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester (74.57 g, 300 mmole) in dry DMF (260 ml_) under argon was stirred efficiently* in a water bath (to maintain approximately RT - may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 ml_, 316 mmole) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.56 g, 90%). |
90% | A suspension of 6-methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester (74.57 g, 300 mmol) in dry DMF (260 mL) under argon was stirred efficiently* in a water bath (to maintain approximately room temperature - may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 mL, 316 mmol) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.6 g, 90%) as an off-white solid which was used without further purification: LC/MS (ES) m/z 312 [MH-H]+ | |
83% | With phosphorus tribromide; In N,N-dimethyl-formamide; at 20℃; for 0.5h;Inert atmosphere; | A suspension of ethyl 6-methoxy-4-oxo-1 ,4-dihydro-1 ,5-naphthyridine-3- carboxylate (6.3 g, 25.4 mmol) in DMF (20 mL) was stirred under N2 at room temperature. Phosphorus tribromide (2.5 mL, 26.7 mmol) was added drop- wise and the reaction mixture was stirred for additional 30'. The mixture was put in an ice-bath and water (120 mL) was added, followed by sat. Na2C03 to pH 7. The solid was filtered under vacuum, washed with water and dried under vacuum. The crude product was purified by NH cartridge (eluent from Cy 100% to Cy/EtOAc 95/5%) to obtain ethyl 4-bromo-6-methoxy-1 ,5- naphthyridine-3-carboxylate (6.6 g, 21 mmol, 83% yield). LC-MS (M-H+) = 31 1 .1 |
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