Structure of 808744-34-5
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CAS No. : | 808744-34-5 |
Formula : | C7H5BrN2 |
M.W : | 197.03 |
SMILES Code : | BrC1=CC2=NC=CN2C=C1 |
MDL No. : | MFCD07778353 |
InChI Key : | OASOJRLJBDCVNU-UHFFFAOYSA-N |
Pubchem ID : | 15098903 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | 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 | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 42.89 |
TPSA ? Topological Polar Surface Area: Calculated from | 17.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.94 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 2.45 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 2.1 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 1.48 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 1.67 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 1.93 |
Log S (ESOL):? ESOL: Topological method implemented from | -3.27 |
Solubility | 0.106 mg/ml ; 0.000536 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -2.46 |
Solubility | 0.688 mg/ml ; 0.00349 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -2.94 |
Solubility | 0.225 mg/ml ; 0.00114 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 | -5.76 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 | 0.0 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) | 1.66 |
* 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 |
---|---|---|
75% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; acetonitrile; at 60℃; for 18h; | Step B: Preparation of 7-(pyridin-3-yl)imidazori.2-a1pyridine:; A suspension of potassium carbonate (0351 g, 2.54 mmol), pyridin-3-ylboronic acid (68.6 mg5 0.558 mmol), 7- bromoimidazo[l52-a]pyridine (0.100 g, 0.508 mmol) and tetrakis(triphenylphosphine) <n="70"/>palladium (0) (29.3 mg, 0.025 mmol) in 6.5 ml of a 1:1 :4.5 mixture of water:dimethylformamide:acetonitrile was degassed thoroughly under a nitrogen atmosphere, and heated at 60 0C for 18 hours. The reaction mixture was poured in water (50 ml) and extracted with dichloromethane and EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated to afford a solid. The solid was purified by silica gel chromatography (eluting with 6% MeOH-chloroform) to afford the desired compound (74.1 mg, 75 % yield). MS APCI (+) m/z 196.3 (M+l) detected. |
75% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; acetonitrile; at 60℃; for 18h; | A suspension of potassium carbonate (0.351 g, 2.54 mmol), pyridine-3-ylboronic acid (68.6 mg, 0.558 mmol), 7-bromoimidazo[l,2-a] pyridine (0.100 g, 0.508 mmol) and tetrakis(triphenylphosphine) palladium (0) (29.3 mg, 0.025 mmol) in 6.5 ml of a 1:1 :4.5 mixture of water:dimethylformamide:acetonitrile was degassed thoroughly under a nitrogen atmosphere, and heated at 60 C for 18 hours. The reaction mixture was poured in water (50 ml) and extracted with dichloromethane and EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated to afford a solid. The solid was purified by silica gel chromatography (eluting with 6% MeOH-chloroform) to afford the desired compound (74.1 mg, 75 % yield). MS APCI (+) m/z 196.3 (M+l) detected. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In water; at 100℃; for 4h; | To a suspension of 4-bromopyridin-2-amine (5.26 g, 30.40 mmol) in water (50 mL) was added 2-chloroacetaldehyde (40% [w/w] in water, 15.24 g, 77.66 mmol). The reaction mixture was stirred at 100 C for 4 h, and adjusted to pH = 10 with a saturated Na2CO, aqueous solution, then extracted with DCM (100 mL c 3). The combined organic phases were washed with brine (100 mL), dried over anhydrous Na2S04, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM (v/v) = 1/100) to give the title compound as yellow oil (5.93 g, yield 100%).MS (ESI, pos. ion) m/z: 197.2 [M+H]+;1H NMR (400MHz, CDCl3) d (ppm): 8.00 (d, j = 7.2 Hz, 1H), 7.82 (d, J = 0.8 Hz, 1H), 7.61 (s, 1H), 7.57 (s, 1H), 6.90 (dd, j= 7.2, 1.7 Hz, 1H). |
100% | In water; at 100℃; for 4h; | To 4-bromopyridin-2-amine (5.26 g, 30.40 mmol)In water (50mL) suspension2-chloroacetaldehyde (40% [w/w] in water, 15.24 g, 77.66 mmol).The reaction mixture was stirred at 100 C for 4 hours.After the reaction,Adjust to pH=10 with a saturated aqueous solution of sodium carbonate.It was then extracted with dichloromethane (100 mL x 3).The combined organic phases were washed with saturated brine (100 mL).Dry over anhydrous sodium sulfate,Filter and concentrate under reduced pressure.The residue obtained is purified by silica gel column chromatography (MeOH/DCM (v/v) = 1/100).The title compound was obtained as a yellow liquid (5.93 g, yield 100%). |
78% | With sodium hydrogencarbonate; In ethanol; for 6h;Reflux; | The compound 2-amino-4-bromopyridine 22 (5.0 g) and 2-chloroacetaldehyde (40%solution, 12 mL, 2.5 eq) was dissolved in absolute ethanol (50 mL)After addition of NaHCO3 (4.89 g, 2.0 eq)Reflux reaction 6h.The organic solvent was removed by vacuum filtration, washed with EA (60 mL), washed with water, saturated with brine, dried over Na2SO4 and dried on a dry column to give brown solid 23 (4.38 g, 78%). |
71% | Example 44; 8-(ftrans)-3-fluoropiperidin-4-yloxy)-2-(7-(pyridin-3-yl)imidazo[1.2-a]pyridin-3-yl)qiotaiotainoluie; Step A: Preparation of 7-bromoimidazo[1.2-a]pyridine:; A solution of 4- bromopyridin-2-amine (1.00 g, 5.78 mmol) and 2-chloroacetaldehyde (50% wt aqueous solution, 1.83 ml5 14.45 mmol) in absolute ethanol (9.5 ml) was refluxed for 12 hours, and then allowed to cool to ambient temperature overnight. The reaction mixture was concentrated under reduced pressure and carefully re-suspended in saturated aqueous bicarbonate solution (100 ml). The resulting mixture was extracted thoroughly with DCM and EtOAc, and the combined organic extracts were dried over anhydrous sodium sulfate and concentrated to afford 1.31 g of a solid. The solid was purified by silica gel chromatography (eluting with 3% MeOH-chloroform) to afford the desired compound (0.808 g5 71 % yield). MS APCI (+) m/z 197.1 and 199.1 (M+l for each isotope) detected. | |
71% | In ethanol; water; at 20℃; for 12h;Heating / reflux; | A solution of 4- bromopyridin-2-amine (1.00 g, 5.78 mmol) and 2-chloroacetaldehyde (50% wt aqueous solution, 1.83 ml, 14.45 mmol) in absolute ethanol (9.5 ml) was refluxed for 12 hours, and then allowed to cool to ambient temperature overnight. The reaction mixture was concentrated under reduced pressure and carefully re-suspended in saturated aqueous bicarbonate solution (100 ml). The resulting mixture was extracted thoroughly with DCM and EtOAc, and the combined organic extracts were dried over anhydrous sodium sulfate and concentrated to afford 1.31 g of a solid. The solid was purified by silica gel chromatography (eluting with 3% MeOH-chloroform) to afford the desired compound (0.808 g, 71 % yield). MS APCI (+) m/z 197.1 and 199.1 (M+l for each isotope) detected. |
63% | With sodium hydrogencarbonate; In ethanol; for 16h;Reflux; | To a stirred solution of 4-bromopyridin-2-amine (5 g, 28.9 mmol, Molekula Biokem Ltd) in EtCH (5OmL), added sodium bicarbonate (7.28 g, 86.7 mmol) and chloroacetaldehyde (5 mL, 115 mmol) and refluxed for 16 h. The reaction mixture was evaporated under vacuum and water (25 mL) was added to the crude mixture. The resulting solution was extractedwith EtOAc (2 x 50 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated. The resulting crude product was purified by flash chromatography. Yield:63% (3.6 g, brown solid). LCMS: (Method B) 199.0 (M +H), Rt. 3.92 mm, 94.50% (Max). |
63% | With sodium hydrogencarbonate; In ethanol; for 16h;Reflux; | To a stirred solution of 4-bromopyridin-2-amine (5 g, 28.9 mmol, Molekula Biokem Ltd) in EtOH (50ml_), added sodium bicarbonate (7.28 g, 86.7 mmol) and chloroacetaldehyde (5 mL, 1 15 mmol) and refluxed for 16 h. The reaction mixture was evaporated under vacuum and water (25 mL) was added to the crude mixture. The resulting solution was extracted with EtOAc (2 x 50 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated. The resulting crude product was purified by flash chromatography. Yield: 63% (3.6 g, brown solid). LCMS: (Method B) 199.0 (M +H), Rt. 3.92 min, 94.50% (Max). |
With sodium hydrogencarbonate; In ethanol; for 17h;Heating / reflux; | 4-Bromo-pyridin-2-ylamine (1 eq, 5.78 mmol, 1 g) is added to a solution of chloroacetic aldehyde (5 eq, 28.9 mmol, 5 ml) in EtOH (25 ml). NaHCO3 (2 eq, 11.6 mmol, 971 g) is then added and the reaction mixture is heated at reflux for 17 h. The solvent is then removed in vacuo and the product is purified by flash column chromatography eluting with 9:1 DCM/MeOH to afford 7-bromo-imidazo-[1,2-a]- pyridine as a brown solid; [M+H]+ = 198 | |
INTERMEDIATE SYNTHESIS; 7-bromo-3-iodoimidazo[ 1 ,2-a]pyridine; (1) 7-bromoimidazo[l,2-a]pyridine.; To a 100 niL round -bottomed flask was added 4-bromopyridin-2-amine (4.0 g, 23.1 mmol), chloroacetaldehyde, 50% in water (14.9 rnL, 116 mmol), and EtOH (25 mL). The resulting reaction mixture was heated at 100 0C under N2 for 3 h. The reaction was cooled to rt and the solvent was concentrated. The residue was redissolved in EtOAc. The organic layer was washed with sat. NaHCObeta (2 x 40 mL), water (2 x 40 mL), brine, dried over MgSO4, and removed solvent. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep, 12O g SiO2, DCM:MeOH=96%:4% to DCM:MeOH (2M NH3)=95%:5%, Flow = 85 niL/min). The solvent was removed in vacuo to afford the desired product as brown solid (3.8 g). MS (ESI pos. ion) m/z: 196.8. Calcd exact mass for C7H5BrN2: 195.9. 1U NMR (300 MHz, CHLOROFORM-J) delta ppm 6.90 (d, J=7.16 Hz, 1 H) 7.57 (s, 1 H) 7.62 (s, 1 H) 7.83 (s, 1 H) 8.00 (d, J=7.16 Hz, 1 H). | ||
18.6 g | In ethanol; water; at 0℃;Reflux; | The compound 2-amino-4-bromopyridine 6 (20.00 g, 116.28 mmol) was dissolved in a mixture of ethanol (300 mL) and water (30 mL).After stirring for 20 minutes under ice bath conditions, when the solution temperature drops to 0 C,40% chloroacetaldehyde (28.60 mL, 174.40 mmol) was added slowly and stirred at reflux overnight.The mixture was filtered with Celite, and then evaporated and evaporated.Washed with water, washed with saturated brine, dried with Na2SO4 and then driedColumn chromatography gave a brown solid 8 (18.60 g, 81%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With triethylamine;tris-(dibenzylideneacetone)dipalladium(0); tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; at 100℃; for 17h; | A solution of7-bromoimidazo[l,2-a]pyridine (0.100 g, 0.508 mmol), tri-o-tolylphosphine, tris(dibenzylideneacetone)dipalladium(0) (47 mg, 0.051 mmol), and 2-tri-n- butylstannylpyridine (0.234 g, 0.508 mmol) in anhydrous DMF (5 ml) was combined at ambient temperature under a nitrogen atmosphere with triethylamine (65 mg, 0.65 mmol). The reaction mixture was heated at 100 0C for 17 hours. The reaction mixture was then allowed to cool, poured in water (40 ml), and extracted with DCM, ether, and EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated to afford a solid. The solid was purified by silica gel chromatography (eluting with 5% MeOH-DCM) to afford the desired compound (38.4 mg, 39% yield). MS APCI (+) m/z 196.3 (M+l) detected |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate;bis(tri-t-butylphosphine)palladium(0); In ethanol; water; toluene; at 75℃; for 2h; | Procedure B1c - Suzuki coupling for heterocvcles.; A solution of 7-Bromo-imidazol[1 ,2-a]pyridine (0.5g, 2.54mmol, 1 equivalent, made according to general procedure A1 using 4-bromo-pyridin-2-ylamine instead of 4-chloro-pyridin-2- ylamine) , 1 -methyl-5-(4,4, 5, 5-tetramethyl-[ 1 , 3, 2]dioxaborolan-2-yl)- 1 H-py razole ( 1.1 g, 5.08mmol, 2 equivalents), bis(tri-t-butylphosphine) palladium (0) (66mg, 0.13mmol, 0.05 equivalents) and potassium carbonate (2.1g, 15.24mmol, 6 equivalents) in ethanol (10ml), toluene (10ml) and water (10ml) was heated at 750C for 2 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was then washed with a saturated brine solution, dried (MgSO4), filtered and the solvent removed by evaporation in vacuo. The residue was purified by column chromatography (Biotage SP4, 25S, flow rate 25ml/min, gradient 0% to 20% methanol in ethyl acetate) to give 7-(2-methyl-2H-pyrazol-3-yl)- imidazo[1 ,2,a]pyridine as a colourless oil (350mg, 70%). MS: [M+H]+ 199. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 120℃; for 0.166667h;Microwave radiation; | 7-Bromo-imidazo-[1,2-a]-pyridine (1 eq, 0.5 mmol, 100 mg) and (3-methylamino carbonylphenyl)boronic acid (1.1 eq, 0.558 mmol, 99.9 mg) are dissolved in DME (3 ml) and water (0.8 ml) and Na2CO3 (3 eq, 1.52 mmol, 161 mg) is added. PdCl2(PPh3)I (0.05 eq, 0.025 mmol, 17.8 mg) is then added and the reaction mixture is heated using microwave radiation at 120C for 10 min. At the completion of this time the solvent is removed in vacuo and the reaction mixture is purified by flash column chromatography eluting with 9:1 DCM/MeOH to yield 3-imidazo[1,2-a]pyridine-7-yl- N-methyl-benzamide as a brown solid; [M+H]+ = 252 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.9% | With N-iodo-succinimide; In N,N-dimethyl-formamide; at 100℃; for 1h; | To a solution of 7-bromoimidazo[l,2-a]pyridine (5.93 g, 30.1 mmol) in DMF (60 mL) was added NIS (9.19 g, 40.8 mmol). The reaction mixture was stirred at 100 C for 1 hour, then cooled down to rt and quenched with water (50 mL), then extracted with DCM (100 mL x 3). The combined organic phases were washed with brine (100 mL), dried over anhydrous Na2S04, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v) = 1/10) to give the title compound as a yellow solid (8.45 g, yield 86.9%).MS (ESI, pos. ion) m/z: 323.0 [M+H]+;1H NMR (400 MHz, CDCl3) d (ppm): 8.02 (d, J= 7.3 Hz, 1H), 7.83 (d, J= 1.2 Hz, 1H), 7.69 (s, 1H), 7.05 (dd, j= 7.3, 1.7 Hz, 1H). |
86.9% | With N-iodo-succinimide; In N,N-dimethyl-formamide; at 100℃; for 1h; | To <strong>[808744-34-5]7-bromoimidazo[1,2-a]pyridine</strong> (5.93 g, 30.1 mmol)Add in DMF (60mL) solutionNIS (9.19 g, 40.8 mmol).The reaction mixture was stirred at 100 C for 1 hour.Then cool to room temperature,The reaction was quenched by the addition of water (50 mL).It was then extracted with DCM (100 mL x 3).Combined organic phase with saturated brine (100 mL)Washed, dried over anhydrous sodium sulfate,Filter and concentrate under reduced pressure.The residue obtained was purified by silica gel column chromatography (EtOAc /EtOAcThe title compound was obtained as a white solid (8.45 g, yield 86.9%). |
With iodine; sodium acetate; In methanol; at 0℃; | (2) 7-bromo-3-iodoimidazo[l,2-a]pyridine.; To a 250 mL round bottomed flask was added 7-bromoimidazo[l,2-a]pyridine (3.8 g, 19.29 mmol), sodium acetate (4.3 g, 52.1 mmol) and MeOH (60 mL). The resulting mixture was cooled to 0 0C followed by adding diiodine (8.3 g, 32.8 mmol). After the addition, ice bath was removed and the mixture was continued to stir for 5 h. The solvent was concentrated. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep, 330 g SiO2, hexanes:acetone= 80%:20%, Flow = 100 mL/min). The solvent was removed in vacuo to afford the desired product as light yellow solid (3.2 g). (ESI pos. ion) m/z: 322.8. Calcd exact mass for C7H4BrIN2: 321.9. 1H NMR (300 MHz, CHLOROFORM-^) delta ppm 7.04 (d, J=7.02 Hz, 1 H) 7.68 (s, 1 H) 7.82 (s, 1 H) 8.01 (d, J=7.31 Hz, I H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58.4% | With rac-diaminocyclohexane; cesium fluoride;copper(l) iodide; In 1,4-dioxane; at 95℃;Inert atmosphere; | 1 equiv. of the oxazolidin-2-one was given together with <strong>[808744-34-5]7-bromoimidazo[1,2-a]pyridine</strong> (1 equiv.), cesium fluoride (2 equiv.) and copper(I) iodide (0.1 equiv.) in a flask. The flask was purged with argon and a solution of cyclohexane-1,2-diamine (0.1 equiv.) in dioxane was added. The reaction was stirred at 95 C. until TLC indicated consumption of the oxazolidin-2-one. After cooling to 45 C. the reaction mixture was filtered through a pad of CELITE, the pad was washed with warm dichloromethane and the solution was concentrated under reduced pressure. The final product was purified via FPLC using a chloroform-methanol gradient (0?10%). Step D:Product obtained from step C (0.376 g, 1.7 mmol), <strong>[808744-34-5]7-bromoimidazo[1,2-a]pyridine</strong> (0.335 g, 1.7 mmol), copper(I) iodide (0.033 g, 0.17 mmol), cesium fluoride (0.52 g, 3.4 mmol), cyclohexane-1,2-diamine (0.021 mL, 0.17 mmol), yield: 0.335 g (58.4%)Overall yield: 8.7%; MS m/z 338.2 (M+H)+; 1H NMR (400 MHz, DMSO-D6): delta 0.92 (t, 3H, J=7.5 Hz); 1.62-1.70 (m, 2H); 3.83-3.87 (m, 2H); 4.12-4.16 (m, H); 4.80-4.84 (m, H); 5.71-5.74 (m, H); 6.89 (d, 2H, J=8.7); 7.26 (d, H, J=7.5 Hz); 7.31-7.38 (m, 3H); 7.48 (br s, H); 7.83 (br s, H); 8.46 (br s, H), HPLC (lambda=214 nm), [B]: rt 11.20 min (95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31.3% | With potassium carbonate; rac-diaminocyclohexane;copper(l) iodide; In 1,4-dioxane; at 95℃;Inert atmosphere; | 1 equiv. of the 1,3-oxazinan-2-one was given together with <strong>[808744-34-5]7-bromoimidazo[1,2-a]pyridine</strong> (1 equiv.), potassium carbonate (2 equiv.) and copper(I) iodide (0.1 equiv.) in a flask. The flask was purged with argon and a solution of cyclohexane-1,2-diamine (0.1 equiv.) in dioxane was added. The reaction was stirred at 95 C. until TLC indicated consumption of the 1,3-oxazinan-2-one. After cooling to 45 C. the reaction mixture was filtered through a pad of CELITE, the pad was washed with warm dichloromethane and the solution was concentrated under reduced pressure. The final product was purified via FPLC using a chloroform-methanol gradient (0?10%). Step D:Product obtained from step C (0.45 g, 1.91 mmol), <strong>[808744-34-5]7-bromoimidazo[1,2-a]pyridine</strong> (0.376 g, 1.91 mmol), copper(I) iodide (0.036 g, 0.19 mmol), potassium carbonate (0.528 g, 3.82 mmol), cyclohexane-1,2-diamine (0.023 mL, 0.19 mmol), yield: 0.210 g (31.3%)Overall yield: 6.1%; MS m/z 352.3 (M+H)+; 1H-NMR (400 MHz, DMSO-d6): delta 0.87-0.91 (m, 3H); 1.58-1.67 (m, 2H); 2.05-2.12 (m, H); 2.49-2.57 (m, H); 3.79-3.82 (m, 2H); 4.20-4.26 (m, H); 4.35-4.40 (m, H); 5.45-5.47 (m, H); 6.81 (d, 2H, J=8.7 Hz); 7.24 (d, 2H, J=8.7 Hz); 7.47 (d, H, J=7.9 Hz); 7.75 (s, H); 7.96 (s, H); 8.10 (s, H); 8.65 (d, H, J=7.9 Hz), HPLC (lambda=214 nm), [B]: rt 9.73 min (100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | Example 687-[4-(4- [(35)- 1 -(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl} -4H- 1 ,2,4-triazol-3- yl)phenyl]imidazo[ 1 ,2-a]pyridinA mixture of 7-bromoimidazo[l,2-a]pyridine (125 mg, 0.634 mmol),£zs(pinacolato)diboron (180 mg, 0.709 mmol), KOAc (250 mg, 2.55 mmol), andPdCl2(dppf) (50 mg, 0.061 mmol) in 1,4-dioxane (3 mL) was stirred at 100 C. 3-(4- Bromophenyl)-4- { [(35)- 1 -(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl} -4H- 1 ,2,4-triazole (230 mg, 0.613 mmol) and 2 M aq. K2C03 (1.5 mL) were added and the reaction mixture was stirred at 100 C overnight. The 1,4-dioxane layer was removed, passed through a plug of Celite and Na2S04, rinsed with 1,4-dioxane (4 mL), and the organic layers concentrated in vacuo. Purification of the residue by reverse phase HPLC (5-45%CH3CN/water with 0.1% TFA), reverse phase HPLC (10-70% CH3CN/water with 0.1% NH4OH), and then reverse phase HPLC (2-40% MeOH/water with 0.08% NH4OH) provided the title compound (36 mg, 13%). MS(ES)+ m/e 413.3 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere; Sealed vial; | Example 145l-[(3S)-l-(Cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2-(4-imidazo[l,2-fl]pyridin- 7-ylphenyl)-5-(trifluoromethyl)-lH-benzimidazole2-(4-Bromophenyl)- 1 - { [(3 S)- 1 -(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl} -5- (trifluoromethyl)-lH-benzimidazole (82 mg, 0.167 mmol) was dissolved in 1,4-dioxane (1.5 mL) in 5-mL microwave vial. Potassium acetate (44.8 mg, 0.457 mmol),4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-l,3,2-dioxaborolane (42.5 mg, 0.167 mmol), andPdCl2(dppf)-CH2Cl2 adduct (6.22 mg, 7.61 umol) were then added with stirring. The vial was purged with nitrogen, sealed, and heated to 100 C for 2 hours. The reaction mixture was allowed to cool to room temperature. 7-Bromoimidazo[l,2-a]pyridine (30 mg, 0.152 mmol), PdCl2(dppf)-CH2Cl2 adduct (6.22 mg, 7.61 umol) and 2 M aqueous potassium carbonate (0.228 mL, 0.457 mmol) were then added. The vial was again purged with nitrogen, sealed and heated at 100 C for 2 hours. The reaction mixture was allowed to cool to room temperature, diluted with water (50 mL), acidified to pH 7 with 1 N HC1, and extracted with DCM (3 x 50 mL). The combined DCM extracts were dried over sodium sulfate and evaporated to dryness. The resulting crude product was dissolved in DMSO and purified by preparative reverse phase hplc. The appropriate fractions were combined and the pH adjusted to 7 with aqueous sodium bicarbonate (saturated) and extracted with DCM (3 x 25 mL). The combined DCM extracts were dried over sodium sulfate and evaporated to dryness to afford 22 mg of the titled compound. (LCMS m/z 529.9, M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 18h;Sealed tube; Inert atmosphere; Microwave irradiation; | In a sealed microwave vial purged with nitrogen, a mixture of 7-bromoimidazo[l,2- ajpyridine (50 mg, 0.254 mmol), bis(pinacolato)diboron (66 mg, 0.260 mmol), potassium acetate (70 mg, 0.713 mmol), and l,l'-bis(diphenylphosphino)ferrocene- palladium(II)dichloride dichloromethane complex (10 mg, 0.012 mmol) in 1,4-dioxane (2 mL) was stirred at 90 C for 18 h to give the boronic ester intermediate, 7-(4 ,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)imidazo[l,2-a]pyridine. The reaction mixture was cooled to room temperature. 9-[(4-bromo-2-fluorophenyl)methyl]-4-cyclopropyl-l-oxa-4,9- diazaspiro[5.5]undecan-3-one (100 mg, 0.237 mmol), l,l'-bis(diphenylphosphino)ferrocene- palladium(II)dichloride dichloromethane complex (10 mg, 0.012 mmol) and 2M aqueous potassium carbonate solution (1 mL, 2 mmol) were added to the reaction mixture and the resulting mixture was stirred at 100 C for 1 h. The reaction was cooled to room temperature, diluted with ethyl acetate (20 mL) and water (5 mL), and the layers were separated. The aqueous layer was extracted with ethyl acetate (20 mL). The organic layers were combined, dried over MgSC^, and concentrated in vacuo. Purifications by silica gel chromatography (0- 10% methanol/ethyl acetate) followed by reverse phase HPLC (10-70% acetonitrile /water + 0.1% NH4OH) provided the title compound as a beige solid (16 mg, 16%). MS(ES)+ m/e 435.1 [M+H]+. | |
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 2h;Inert atmosphere; | A mixture of <strong>[808744-34-5]7-bromoimidazo[1,2-a]pyridine</strong> (40 mg, 0.164 mmol), (0842) 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (40 mg, 0.136 mmol), KOAc (93 mg, 0.34 mmol) and Pd(dppf)Cl2.DCM (14 mg, 0.019 mmol) in dioxane (2 mL) was stirred at 90 oC for 2 h under N2 atmosphere. The reaction was concentrated in vacuo and the crude mixture of 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine was used in the next step without purification. LC-MS m/z: 245.2 [M+H]+. tR = 1.17 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
244 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; at 110℃; for 12h;Inert atmosphere; | b) 6-(Imidazo[1,2-a]pyridin-7-yl)-1,3,3-trimethylindolin-2-one Through a suspension of 1,3, 3-trimethyl-6-(4,4,5 ,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)indolin- 2-one (300 mg, 896 imol), 7-bromoimidazo[1,2-alpyridine (F.P. Marmsaeter et al.,W02008121687; 212 mg, 1.08 mmol) and Na2CO3 (2M, 896 tl, 1.79 mmol) in dioxane (4 ml) was bubbled argon for 5 minutes. [1,1 ?-Bis(diphenylphosphino)ferrocenel dichloropalladium(II) (32.8 mg, 44.8 imol) was added and argon was bubbled through again for 5 minutes. The reaction mixture was heated to 110 C for 12 hours. The solvent was evaporated and the residue was purified by silica gel chromatography using ethyl acetate heptane and dichloromethane methanol ammonia as eluent. The title compound was obtained as light red solid (244 mg). MS ESI (mz): 292.2 [(M+H)i.1H NMR (CDC13, 300 MHz): oe = 8.20 (dd, J=0.8, 7.1 Hz, 1H), 7.87 - 7.80 (m, 1H), 7.69 (d,J=1.2 Hz, 1H), 7.62 (s, 1H), 7.38 - 7.28 (m, 2H), 7.14 - 7.04 (m, 2H), 3.29 (s, 3H), 1.42 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Palladium acetate (0.021 g, 0.094 mmol) and triphenylphosphine (0.10 g, 0.38 mmol) were combined in a flask in 1,4-dioxane (6.0 mL). After stirring for 30 mi DMF (5.7 g, 6.0 mL, 78 mmol), tert-butyl 4-[4-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)phenoxyj piperidine- 1- carboxylate (0.75 g, 1.9 mmol), 7-bromoimidazo[1,2-ajpyridine (0.44 g, 2.2 mmol) and aq. Na2CO3 (0.5 M) (12.0 mL, 6.0 mmol) were added and the flask was heated under nitrogen at 90C overnight. The mixture was diluted with water (60 mL) then extracted with EtOAc (3x50 mL). The organic extracts were combined, washed with brine (50 mL), dried over sodium sulfate filtered and concentrated in vacuo. The residue was dissolved in EtOAc (40 mL) then treated with 2M HC1 in ether (1.5 mL) with stirring. The resultant solids were collected by filtration, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; at 80℃; for 18.0333h;Inert atmosphere; Sealed tube; | To a solution of 4-[(4-bromophenyl)methyl]-1 ,4-thiazinane 1,1-dioxide 1-5 (303 mg, 1 .0mmol) in THF (2 mL)was added bis(triphenylphosphine)palladium dichloride (35 mg, 0.05mmol) and Cul (19 mg, 0.10 mmol), with nitrogen bubbling through the mixture. TEA (1.4 mL, 10 mmol), followed by trimethylsilylacetylene (200 pL, 1 .4 mmol) were added, still under bubbling of nitrogen. After 2 mm, the vial was sealed and the reaction was stirred for 18 h at 90C. The reaction mixture was diluted with DCM (10 mL) and washed withwater (10 mL) and brine (10 mL) before passing through a phase separator cartridge (Biotage). The solvent was removed in vacuo to give a residue which was was purified by flash column chromatography (Biotage Isolera Four, lOg KP-Sil column, 1% EtOAcI isohexane to 50% EtOAc I isohexane) to afford the title compound as a brown oil (50 mg, 0.16 mmol, 16%).:_Procedure similar to that described for 4-(4-trimethylsilanylethynyl-benzyl)-thiomorpholine-1,1-dioxide 1-9 except that <strong>[808744-34-5]7-bromo-imidazo[1,2-a]pyridine</strong> (250 mg, 1.26 mmol) was usedand the reaction stirred at 80C instead of 90C. The method afforded the title compound(148 mg, 0.68 mmol, 55%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 100℃; for 12h; | The compound 7-bromoimidazo [1,2-a] pyridine 23 (487.9 mg, 1.0 eq)N-methylpiperazine (0.83 mL, 3.0 eq), Pd2 (dba) 3 (45.8 mg, 2%), Xantphos (86.8 mg, 6%)And t-BuONa (0.36 g, 1.5 eq) were dissolved in toluene (3.5 mL)Reaction at 100 deg.] C 12h.(10%) of silica gel (1-10% MeOH / DCM) to afford white solid 24 (476 mg, 88.0%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.88 g | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In water; at 80℃; | Compound 37 (1.3 eq) was dissolved in DMF (169.3 mL)7-Bromoimidazo [1,2-a] pyridine (3.48 g) was added,1N Na2CO3 aqueous solution (26.64 mL) and Pd (dppf) Cl2 DCM (0.05 eq) were added, and the reaction was then reacted at 80C overnight.Celite filtration, rotary evaporation in vacuo the organic solvent after column chromatography (2-10% MeOH / DCM) to give a white solid 31 (4.88g, 72%). |
Tags: 808744-34-5 synthesis path| 808744-34-5 SDS| 808744-34-5 COA| 808744-34-5 purity| 808744-34-5 application| 808744-34-5 NMR| 808744-34-5 COA| 808744-34-5 structure
A269658 [1019020-14-4]
7-Bromoimidazo[1,2-a]pyridine-3-carbaldehyde
Similarity: 0.84
A422408 [116355-18-1]
6-Bromo-7-methylimidazo[1,2-a]pyridine
Similarity: 0.83
A160356 [946000-27-7]
4-Bromo-N,N-dimethylpyridin-2-amine
Similarity: 0.83
A269658 [1019020-14-4]
7-Bromoimidazo[1,2-a]pyridine-3-carbaldehyde
Similarity: 0.84
A422408 [116355-18-1]
6-Bromo-7-methylimidazo[1,2-a]pyridine
Similarity: 0.83
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