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Structure of 1532-71-4
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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. : | 1532-71-4 |
Formula : | C9H6BrN |
M.W : | 208.05 |
SMILES Code : | BrC1=NC=CC2=CC=CC=C12 |
MDL No. : | MFCD00234478 |
InChI Key : | YWWZASFPWWPUBN-UHFFFAOYSA-N |
Pubchem ID : | 640963 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H301-H318-H401 |
Precautionary Statements: | P280-P273-P301+P310-P305+P351+P338 |
Class: | 8(6.1) |
UN#: | 2923 |
Packing Group: | Ⅲ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 49.44 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.08 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.27 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.82 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.86 |
Solubility | 0.0285 mg/ml ; 0.000137 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.22 |
Solubility | 0.127 mg/ml ; 0.000609 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.56 |
Solubility | 0.00574 mg/ml ; 0.0000276 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 |
-5.25 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) |
1.62 |
* 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 |
---|---|---|
Example B-1A-2 <Synthesis of the mononuclear ruthenium complex (B-M-2a) [[(BiBzlm)Ru(1,1'-biq)2]] (the complex of the formula (2-3) in which R02s present on a pyridine ring are bonded to each other to form a benzene ring) according to the synthesis method (2-A)> Under nitrogen atmosphere, nickel chloride hexahydrate (4.61 g, 19.4 mmol), triphenylphosphine (20.2 g, 76.9 mmol) and N,N-dimethylformamide (90 mL) were placed into a 300 mL three-necked flask, and then zinc powder (1.26 g, 19.2 mmol) was added. The mixture was stirred for 75 minutes at 65 °C. And then, <strong>[1532-71-4]1-<strong>[1532-71-4]bromoisoquinoline</strong></strong> (4.00 g, 19.2 mmol) was added, and the mixture was stirred for 5 hours at 140 °C. After the completion of the reaction, the zinc powder was filtrated off, and the filtrate was concentrated under reduced pressure. And then, dichloromethane (50 mL) and 7percent aqueous ammonia (120 mL) were added to the resultant concentrate, and the mixture was stirred for 30 minutes at room temperature. And then, nickel was removed from the mixture with dichloromethane/7 percent aqueous ammonia, and the desired product was transferred into an aqueous phase with diethyl ether/9 mol/l hydrochloric acid to remove triphenylphosphine. And then, the solution was neutralized with 5 mol/l aqueous sodium hydroxide solution, and the desired product was extracted with dichloromethane. After concentration under reduced pressure, the product was recrystallized with methanol, and 1,1'' biisoquinoline (1,1'-biq) (1.52 g) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With phosphorus tribromide; | Example 13 1-Bromoisoquinoline A mixture of 9.0 g of 1-hydroxyisoquinoline and 40 ml of phosphorus tribromide is inserted for 15 minutes into a preheated oil bath at 135oC. The resulting 2 layers are cooled and concentrated in vacuo. The residue is treated with ice, water, and sodium carbonate. The reaction mixture is extracted with chloroform, dried over sodium sulfate and concentrated. The product is purified by column chromatography, yielding 6.8 g of pale yellow crystals, mp 41-43oC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; at 80℃; for 18h; | A solution of <strong>[1532-71-4]1-<strong>[1532-71-4]bromoisoquinoline</strong></strong> (0.35 g, 1.68 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate (US 2004/0186103) (0.5 g, 1.68 mmol), dichloro(1,1-bis(diphenylphosphino)ferrocene)palladium(II) (0.065 g, 0.05 mol equiv.) and potassium carbonate (0.66 g, 5.0 mmol) in 1,2-dimethoxyethane (10 mL) was heated at 80 °C for 18 hours. The reaction mixture was allowed to cool and then evaporated under reduced pressure. The residue was purified' by column chromatography on silica gel eluting with ethyl acetate: pentane 50 : 50 to afford the title compound as a pale yellow oil, 0.14 g. LRMS (APCI+): m/z [M+H]+ 311 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; ammonium chloride; In tetrahydrofuran; ethanol; N,N-dimethyl-formamide; | EXAMPLE 2 5-Isoquinolinecarboxaldehyde To a solution of n-butyllithium (19.3 mL of 2.5M in hexanes, 48 mmol) in a mixture of ether (80 mL) and THF (80 mL) at -78° C. was added dropwise a solution of <strong>[1532-71-4]bromoisoquinoline</strong> (5.0 g, 24 mmol) in THF (10 mL). The reaction mixture was stirred at -78° C. under argon for 30 minutes. Following the general procedures described by Pearson, et al., in J. Heterocycl. Chem., Vol. 6 (2), pp. 243-245 (199), a solution of DMF (3.30 g, 45 mmol) in THF (10 mL) was cooled to -78° C. and quickly added to the isoquinolyllithium solution. The mixture was stirred at -78° C. for 15 minute. Ethanol (20 mL) was added followed by saturated NH4Cl solution. The resulting suspension was warmed to room temperature. The organic layer, combined with the ether extraction layer, was dried over Na2SO4. A pale yellow solid (2.4 g, 15 mmol, 64percent yield) was obtained from chromatography (SiO2 Type-H, 50percent EtOAc in hexanes) and recrystallization (ethanol): mp 114-116° C.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 50℃; for 12h; | Stage A: 1 -(2-methoxyphenyl)isoquinoline.A solution of <strong>[1532-71-4]1-<strong>[1532-71-4]bromoisoquinoline</strong></strong> (2.06 g, 10 mmol), prepared as described in EuropeanJournal of Organic Chemistry 2002, 4181-4184, 2-methoxyphenylboronic acid (2.79 g, 10 mmol), Pd(PPh3)4 (5percentmol), K2CO3 (5g) in DMF/water (3/1) is stirred at 500C for 12 hours.The reaction mixture is then pored on water (150 mL). The aqueous phase is extracted with EPO <DP n="84"/>ethyl acetate (3xl00mL). The combined organic layers are washed with water (3x200mL).The organic phase is dried over magnesium sulfate and evaporated under vacuum to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; | 2. The starting material was prepared by reaction of <strong>[1532-71-4]1-<strong>[1532-71-4]bromoisoquinoline</strong></strong> with trimethyloxonium tetrafluoroborate in CH2 Cl2 to give 1-bromo-2-methylisoquinolinium tetrafluoroborate, m.p. 162°. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide; | 5. The starting material was prepared by reaction of <strong>[1532-71-4]1-<strong>[1532-71-4]bromoisoquinoline</strong></strong> with HBr to give 1,4-di<strong>[1532-71-4]bromoisoquinoline</strong>, m.p. 95°-96°, followed by reaction of this compound with trimethyloxonium tetrafluoroborate in CH2 Cl2 to give 1,4-dibromo-2-methylisoquinolinium tetrafluoroborate; n.m.r. in solvent A: 3.5(s, 3H); 7.2-8.4(m, 5H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In concentrated H2 SO4; | 8. The starting material was prepared by reaction of <strong>[1532-71-4]1-<strong>[1532-71-4]bromoisoquinoline</strong></strong> in concentrated H2 SO4 at 0° with KNO3. The reaction mixture was worked up with water, NaHCO3 and EtOAc to give 1-bromo-5-nitro isoquinoline, m.p. 187°-8°. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In water; | EXAMPLE 12 A solution of 11.3 g. of 1-methylpiperidin-4-one in 120 ml. of ether is added dropwise to a stirred isoquinolyl-1-lithium solution, freshly prepared from 20.8 g. of <strong>[1532-71-4]1-<strong>[1532-71-4]bromoisoquinoline</strong></strong> and n-butyllithium in 400 ml. of ether, at 0°, under dry nitrogen. The mixture is stirred for 2 hours more at 0°. Water (50 ml.) and then 100 ml. of 5percent hydrochloric acid are added dropwise to decompose the lithium 1-methyl-4-(1-isoquinolyl)-piperidin-4-olate formed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; at 80℃; for 24h; | Place 2-<strong>[1532-71-4]bromoisoquinoline</strong> (20 g, 1 eq) in a dry 1000 ml two-necked flask.Phenylboronic acid (12.3 g, 1.05 eq), Pd (PPh3) 4 (5.55 g, 0.05 eq)And sodium carbonate (30.5 g, 3 eq), then dioxane (500 mL),The reaction was heated to 80 C and stirred for one day.Then, the reaction solution was spun dry, separated into water and dichloromethane, and the organic phase was dried.Purification by column to obtain white intermediate C(Yield 96%). |
79% | With potassium phosphate; In ethanol; water; at 100℃; for 8h; | General procedure: A dried round bottomed flask equipped with a magnetic stirring bar was charged with 10mg Polymer anchored-Pd(II) D catalyst (PS-NPPZ-Pd) (0.0045mmol/Pd), 2-halopyridine (0.5mmol), phenylboronic acid (0.6mmol) and K3PO4 (1.0mmol) were added to a reaction vessel. The mixture was stirred in 4mL of H2O: EtOH (1:1) at 100C for 8h and then cooled to room temperature. The catalyst was filtered and the filtrate was extracted with ethyl acetate (3×10mL). The combined organic layers were extracted with water, and dried over anhydrous Na2SO4. The organic layers were evaporated under reduced pressure and the resulting crude product was purified by column chromatography by using ethyl acetate/hexane (10:90) as eluent to give the corresponding coupled products. The products were characterized by 1H NMR, 13C NMR and HRMS analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With caesium carbonate;palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene;Inert atmosphere; Reflux; | Example 116-(5-(isoquinolin- 1 -ylamino)-2-methylphenyl)-2-(4-(4-methylpiperazin- 1 - ynphenylamino -7.8-dihydropyrido[4.3-dlpyrimidin-5(6H -oneA mixture of 2,2'-Bis(diphenylphosphino)l,r-binaphthyl [BINAP] (28.00 mg, 0.0451 mmol) and Palladium(II)acetate [Pd(OAc)2] (5.00 mg,0.022 mmol) in dry toluene (3ml) was stirred vigorously and nitrogen was bubbled through the suspension for 30 minutes. To this, 6-(5-amino-2-methylphenyl)-2-(4-(4- methylpiperazin- l-yl)phenylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)- one [45](200 mg, 0.451 mmol), 1 -<strong>[1532-71-4]bromoisoquinoline</strong> (1 12.60 mg, 0.541 mmol) and dry cesium carbonate (443.0 mg, 1.352mmol) was added. Nitrogen was bubbled through for another 30 minutes; the mixture was allowed to 15 reflux overnight. The mixture was cooled, diluted with ethyl acetate, water was added and the layers separated. The aqueous layer was extracted with ethyl acetate and the two organic extracts were combined. The organics were washed with brine, then dried (sodiumsulfate), filtered and concentrated. Further purification by silica gel chromatography using 5-10percent ethyl acetate / hexane as eluent provided 6-(5-(isoquinolin- 1 -ylamino)-2-methylphenyl)-2-(4-(4-methylpiperazin- 1 - yl)phenylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one [60] as a yellow solid [Yield:-223 mg, 87.0percent]. |