Structure of 7205-46-1
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CAS No. : | 7205-46-1 |
Formula : | C7H6ClN3 |
M.W : | 167.60 |
SMILES Code : | CN1C=NC2=C1C=C(Cl)N=C2 |
MDL No. : | MFCD16657937 |
InChI Key : | RUVZGKRCLXIBFX-UHFFFAOYSA-N |
Pubchem ID : | 13032381 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 43.8 |
TPSA ? Topological Polar Surface Area: Calculated from |
30.71 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.33 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.62 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.7 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.58 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.37 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.32 |
Solubility | 0.798 mg/ml ; 0.00476 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.58 |
Solubility | 4.45 mg/ml ; 0.0265 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.71 |
Solubility | 0.328 mg/ml ; 0.00195 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 |
-6.38 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) |
1.7 |
* 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 |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos; In 1,4-dioxane; at 120.0℃; for 5h;Inert atmosphere; | A degassed mixture of the amine (1 eq, 200 mg), 6-chloro-l -methyl- lH-imidazo[4,5- c]pyridine (1 eq, 144 mg), Cs2C03 (2 eq, 561 mg), Xphos (0,15 eq, 62 mg) and Pd2(dba)3 (0,1 eq, 79 mg) in dry 1.4-dioxane (5 mL) was heated at 120C for 5 h. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3 x). The combined organics were dried, concentrated and the residue was purified by silica chromatography (EtOAc/cyclohexane; 0:100 to 50:50) to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium diacetate; caesium carbonate; XPhos; In toluene; at 100.0℃; for 16h; | A mixture of the aniline (1.1 eq, 106 mg), 6-chloro-l -methyl- lH-imidazo[4,5-c]pyridine (1 eq, 100 mg), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (0.3 eq, 86 mg), palladium(II) acetate (0.1 eq, 13.5 mg) and CS2CO3 (3 eq, 391 mg) in toluene (5 mL) was stirred at 100 C for 16 h. The reaction mixture was filtered on Celite, the filtrate concentrated and the residue purified by silica chromatography (EtOAc /cyclohexane; 0:100 to 100:0) to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With trimethyl orthoformate; at 100.0℃; for 3h; | 11.9.2 Typical example: Synthesis of 6-chloro-1-methyl-1H-imidazo[4,5-c]pyridine 2-Chloro-4-methylamino-5-aminopyridine (3.0 g, 19.0 mmol), trimethyl ortho formate (50 mL) and formic acid (1.0 mL) were stirred at 100 C for 3 h. The reaction was cooled to ambient temperature and the solvents removed under vacuum. The residue was poured into NaHCO3 solution and then extracted with AcOEt. The combined organic layers were washed with water, followed by brine and then dried over Na2SO4. The solvents were removed under vacuum to give a brown solid, which was purified by column chromatography (30% AcOEt/DCM) to give the target product as a pale brown solid (2.7 g, 85%). 1H NMR (400 MHz, DMSO) delta (ppm): 8.75 (1 H, d, J = 0.89 Hz), 8.39 (1 H, s), 7.84 (1 H, d, J = 0.90 Hz), 3.86 (3 H, s). LC-MS Rt = 1.97 min; [M+H]+ 168. |
With orthoformic acid triethyl ester; at 100.0℃; for 4h; | To a stirred solution of 6-Chloro-N-methyl-pyridine-3, 4-diamine (22 mmol) in trimethyl orthoformate (25 mL) was added formic acid (1 mL) and was heated ay 100C for nearly 4 h when TLC showed the completion of reaction. The reaction was allowed to cool to room temperature and water (50 mL) was added and the mixture was extracted with ethyl acetate (4x50 mL), the combined organic layers were washed with aq. NaHC03 solution, dried over anhydrous sodium sulphate and concentration under reduced pressure gave the desired product Intermediate 2. [00266] 'H-NMR (400 MHz, DMSO-i): delta 3.84 (s, 3H), 7.83 (s, 1H), 8.39 (s, 1H), 8.74 (s, 1H). [00267] Mass (M+l): w/z 168. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In 1,4-dioxane; at 110.0℃; for 16h; | A degassed mixture of the amine (1 eq, 236 mg), 6-chloro-l -methyl- lH-imidazo[4,5- c]pyridine (1 eq, 150 mg), Cs2C03 (2 eq, 583 mg), BINAP (0.3 eq, 167 mg) and Pd2(dba)3 (0.1 eq, 82 mg) in dry 1.4-dioxane (3 mL) was heated at 110C for 16 h. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3 x). The combined organics was dried, concentrated and the residue was purified by silica chromatography (MeOH/DCM; 0:100 to 5:95) to give the desired compound |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos; In N,N-dimethyl-formamide; at 110.0℃; for 18h; | A degassed mixture of the amine (1 eq, 28 mg), 6-chloro-l-methyl-lH-imidazo[4,5- c]pyridine (1 eq, 27 mg), CS2CO3 (2.5 eq, 132 mg), Xphos (0.3 eq, 23 mg) and Pd2(dba)3 (0.1 eq, 15 mg) in dry DMF (1 mL) was heated at 110C for 18 h. Water was added and the reaction mixture was extracted with EtOAc (3 x). The combined organics were dried, concentrated and the residue was purified by silica chromatography (MeOH/EtOAc; 0:100 to 10:90) to give the desired compound |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 100.0℃; for 18h; | A degassed mixture of the amine (1 eq, 67 mg), 6-chloro-l-methyl-lH-imidazo[4,5- c]pyridine (1 eq, 59 mg), Cs2C03 (2.5 eq, 288 mg), BetaGammaNuAlphaRho (0.3 eq, 66 mg) and Pd2(dba)3 (0.1 eq, 32 mg) in dry DMF (2 mL) was heated at 100C for 18 h. Water was added and the reaction mixture was extracted with EtOAc (3 x). The combined organics were dried, concentrated and the residue was purified by prep arative HPLC give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 110.0℃; for 18h; | A degassed mixture of the amine (1.1 eq, 119 mg), 6-chloro-l -methyl- lH-imidazo[4,5- c]pyridine (1 eq, 98 mg), CS2CO3 (2 eq, 378 mg), Xphos (0.3 eq, 83 mg) and palladium(II) acetate (0.1 eq, 13 mg) in dry toluene (5 mL) was heated at 110C for 18 h. The mixture was filtered through Celite and concentrated. The residue was purified by silica chromatography (MeOH/DCM; 0:100 to 10:90) to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dibenzylideneacetone bis(triphenylphiosphine) palladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In N,N-dimethyl-formamide; at 120.0℃; for 16h; | A mixture of 6-chloro-l -methyl- lH-imidazo[4,5-c]pyridine (84 mg, 0.5 mmol), 7-methyl- 2,3-dihydrobenzo[6][l,4]dioxin-6-amin e ( 1 24 mg , 0 . 7 5 mm o l ) , d ib e nzy l i d en e ac e t o n e bis(triphenylphiosphine) palladium (0) (23 mg, 0.025 mmol), 4,5-bis(diphenylphosphino)-9,9- dimethylxanthene (29 mg, 0.05 mmol), sodium teri-butoxide (72 mg, 0.75 mmol) and DMF (1.5 mL) was stirred at 120 C for 16 h. The reaction mixture was allowed to cool to room temperature, filtered and the solvent removed in vacuo. The crude product was purified by preparative HPLC to give the desired compound. [00284] NMR delta (ppm)(CHCl3-d): 8.64 (1 H, s, ArH), 7.68 (1 H, s, ArH), 6.93 (1 H, s, ArH), 6.79 (1 H, m, ArH), 6.39 (1 H, s, NH), 6.34 (1 H, s, ArH), 4.26-4.29 (4 H, m, CH2), 3.67 (3 H, s, CH3), 2.17 (3 H, s, CH3). [00285] LCMS (1 Ocm ESI Bicarb MeCN) tR 2.48 (min) m/z 297 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 110.0℃; for 16h;Inert atmosphere; | The corresponding amine (0.58 mmol) is added to a solution of 6-chloro-l -methyl- 1H- imidazo[4,5-c]pyridine (intermediate 2) (0.45 mmol) and cesium carbonate (0.62 mmol) in dioxane (3 mL). Degassing is done for 5 min, followed by addition of a solution previously sonicated for 10 min of Xantphos (0.06 eq), Pd2(dba)3 (0.03eq) in dioxane (1 mL) under nitrogen. The reaction heated at 110C for 16 h. After completion, water and DCM are added and this mixture is filtered through a phase separator. The organic layers are concentrated under reduced pressure. The crude product is purified by preparative HPLC to afford the expected compound. | |
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 110.0℃;Inert atmosphere; | In a microwave vial was introduced Intermediate 2 (150mg, 0.895mmol), the 2-ethyl aniline (0.14mL, 1.163 mmol) and CS2CO3 (408.2mg, 1.253mmol) in 1,4-dioxane (4 mL). The reaction mixture was degassed with N2 during 10 min. A mixture of Pd2(dba)3 (24.6mg, 0.027mmol) and xantphos (31.1mg, 0.054mmol) in 1,4-dioxane (2 mL) was sonicated and then added under N2 to the reaction mixture. The reaction mixture was degassed with N2 for another 10 min. The vial was capped and the mixture was stirred at 110C overnight. The reaction mixture was concentrated in vacuo, the crude was then purified by flash column chromatography on silica gel using DCM / MeOH (gradient 100 to 95/5) afforded the (2-Ethyl-phenyl)-(l-methyl-lH-imidazo[4,5-c]pyridin-6-yl)-amine. LC-MS : [M+H]+ : 253.33. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In 1,4-dioxane; for 15h;Reflux; | To a solution of 6-chloro-l -methyl- lH-imidazo[4,5-c]pyridine (intermediate 2) (14.9 mmol) in dioxane (100 mL) is added the corresponding aniline (22.4 mmol), cesium carbonate (22.4 mmol), BINAP (0.9mmol) and tris(dibenzylideneacetone)dipalladium (0.45 mmol). The reaction mixture is refluxed for 15 h, filtrated on celite, evaporated to dryness and purified on silica gel to give the expected product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos; In 1,4-dioxane; at 100.0℃; for 24h;Inert atmosphere; | To stirred degassed (N2) 1,4-dioxane (10 mL) is added 4-Aryl-2-Ethylaniline obtained in step i) (2.00 mmol), 6-chloro- 1 -methyl- lH-imidazo[4,5-c] p yri d i n e ( 3 03 m g , 1 . 8 mm o l ) , tris(dibenzylideneacetone)dipalladium(0) (82 mg, 0.09 mmol), 2-dicyclohexylphosphino-2',4',6'- triisopropylbiphenyl (86 mg, 0.18 mmol) and sodium teri-butoxide (260 mg, 2.7 mmol). The reaction mixture is heated to 100C for 1 d, cooled to room temperature, filtered through Celite and washed through with DCM. The reaction mixture is washed with water and the layers are separated and the aqueous layer further extracted with DCM. The organics are combined, dried (hydrophobic filter) and concentrated in vacuo and the resulting residue is purified by column chromatography using silica gel. The fractions containing product are combined and concentrated in vacuo to give the final product (2- Ethyl-4-aryl-phenyl)-(3-methyl-3H-benzoimidazol-5-yl)-amine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In 1,4-dioxane; at 90.0℃; for 16h; | A mixture of 6-chloro-l-methyl-lH-imidazo[4,5-c]pyridine (100 mg, 0.60 mmol), 7-ethyl- 2,3-dihydrobenzo[6][l,4]dioxin-6-amine (160 mg, 0.90 mmol), tris(dibenzylideneacetone)- dipalladium(O) (27 mg, 0.03 mmol), sodium tert-butoxide (86 mg, 0.90 mmol), 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (34 mg, 0.06 mmol) and dioxane (5 mL) was stirred at 90 C for 16 h. The reaction mixture was allowed to cool to room temperature, filtered and concentrated in vacuo. The crude product was purified by column chromatography using silica gel and eluting with 0 - 10% MeOH in DCM to give the desired compound. [00295] NMR delta (ppm)(DMSO-d6): 8.43 (1 H, d, ArH), 7.98 (1 H, s, ArH), 7.69 (1 H, s, ArH), 6.88 (1 H, s, ArH), 6.73 (1 H, s, NH), 6.44 (1 H, d, ArH), 4.22 (4 H, s, CH2), 3.65 (3 H, s, CH3), 2.56- 2.50 (2 H, q, CH2), 1.06 (3 H, t, CH3). [00296] LCMS (15cm_Formic_ASCENTIS_HPLC_CH3CN) tR 7.32 (min) m/z 311 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In 1,4-dioxane; at 90.0℃; for 24h;Inert atmosphere; | To stirred degassed (N2 (g)) dioxane (3 mL) was added 6-chloro-l-methyl-lH-imidazo[4,5- c]pyridine (219 mg, 1.31 mmol), 2-ethyl-4-fluoroaniline (200 mg, 1.44 mmol), sodium-tert-butoxide (189 mg, 1.97 mmol), tris(dibenzylideneacetone)dipalladium(0) (60 mg, 0.066 mmol) and 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (76 mg, 0.131 mmol). The reaction mixture was heated to 90C for 1 d. The reaction mixture was filtered through celite, washed through with EtOAc and partitioned between EtOAc and water. The layers were separated and the aqueous layer extracted with EtOAc, the organics were combined and dried (MgSO i), filtered and concentrated in vacuo to give the desired compound. For analytical purpose, a 100 mg sample was purified by preparative HPLC to give the desired compound. [00301] NMR delta (ppm)(DMSO-d6): 8.45 (1 H, s, NH), 8.01 (1 H, s, ArH), 7.87 (1 H, s, ArH), 7.46- 7.39 (1 H, m, ArH), 7.10-7.05 (1 H, m, ArH), 7.03-6.96 (1 H, m, ArH), 6.55 (1 H, d, ArH), 3.67 (3 H, s, CH3), 2.67-2.57 (2 H, m, CH2), 1.16-1.07 (3 H, m, CH3). [00302] LCMS (lOcm ESCI Bicarb MeCN) tR 2.80 (min) m/z 271 (MH+). | |
With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In 1,4-dioxane; at 90.0℃; for 24h;Inert atmosphere; | To stirred degassed (N2) 1,4-dioxane (3 mL) was added 6-chloro-l -methyl- lH-imidazo[4,5- c]pyridine (219 mg, 1.31 mmol), 2-ethyl-4-fluoroaniline (200 mg, 1.44 mmol), sodium-fert-butoxide (189 mg, 1.97 mmol), tris(dibenzylideneacetone)dipalladium(0) (60 mg, 0.066 mmol) and 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (76 mg, 0.131 mmol). The reaction mixture was heated to 90C for 1 d. The reaction mixture was filtered through Celite, washed through with EtOAc and partitioned between EtOAc and water. The layers were separated and the aqueous layer extracted with EtOAc, the organics were combined and dried (MgSO i), filtered and concentrated in vacuo to give the desired compound, which was used in the next step without further purification. A 100 mg sample was purified by preparative HPLC to give the desired compound. NMR delta (ppm)(DMSO-d6): 8.45 (1 H, s, NH), 8.01 (1 H, s, ArH), 7.87 (1 H, s, ArH), 7.46-7.39 (1 H, m, ArH), 7.10-7.05 (1 H, m, ArH), 7.03-6.96 (1 H, m, ArH), 6.55 (1 H, d, ArH), 3.67 (3 H, s, CH3), 2.67-2.57 (2 H, m, CH2), 1.16-1.07 (3 H, m, CH3). LCMS (lOcm ESCI Bicarb MeCN) Rt 2.80 (min) m/z 271 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6-Chloro-l-methyl-lH-imidazo[4,5-c]pyridine (2.52 g, 0.015 mol) was stirred with 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (0.86 g, 0.0015 mol), sodium-tert-butoxide (2.16 g, 0.0225 mol) and 4-(4-methoxybenzyloxy)-2-methylaniline (3.68 g, 0.015 mol) in dry dioxane (50 mL) under N2 (g) for 30 minutes. Tris(dibenzylideneacetone)dipalladium(0) (0.68 g, 0.00075 mol) was added and the mixture was stirred at 100C for 4.5 h. The mixture was concentrated in vacuo and the residue was treated with water (50 mL) and extracted into EtOAc (2 x 300 mL). The combined extracts were washed with brine, dried (MgSO i), filtered and concentrated in vacuo to give a solid which was recrystalised from isopropanol to give the desired compound. [00306] NMR delta (ppm)(DMSO-d6): 8.43 (1 Eta, d, ArH), 7.98 (1 H, s, NH), 7.75 (1 H, s, ArH), 7.39 (2 H, d, ArH), 7.27 (1 H, d, ArH), 7.00-6.90 (3 H, m, ArH), 6.82 (1 H, dd, ArH), 6.38 (1 H, d, ArH), 5.00 (2 H, s, CH), 3.77 (3 H, s, CH3), 3.64 (3 H, s, CH3), 2.17 (3 H, s, CH3). | ||
With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In 1,4-dioxane; at 100.0℃; for 4.5h;Inert atmosphere; | 6-Chloro-l-methyl-lH-imidazo[4,5-c]pyridine (2.52 g, 0.015 mol) was stirred with 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (0.86 g, 0.0015 mol), sodium tert-butoxide (2.16 g, 0.0225 mol) and 4-(4-methoxybenzyloxy)-2-methylaniline (3.68 g, 0.015 mol) in dry 1,4-dioxane (50 mL) under N2 (g) for 30 min. Tris(dibenzylideneacetone)dipalladium(0) (0.68 g, 0.00075 mol) was added and the mixture was stirred at 100C for 4.5 h. The mixture was concentrated in vacuo and the residue was treated with water (50 mL) and extracted into EtOAc (2 x 300 mL). The combined extracts were washed with brine, dried (MgSO i), filtered and concentrated in vacuo to give a brown solid which was recrystalised from isopropanol to give the desired compound. NMR delta (ppm)(DMSO-d6): 8.43 (1 H, d, ArH), 7.98 (1 H, s, NH), 7.75 (1 H, s, ArH), 7.39 (2 H, d, ArH), 7.27 (1 H, d, ArH), 7.00-6.90 (3 H, m, ArH), 6.82 (1 H, dd, ArH), 6.38 (1 H, d, ArH), 5.00 (2 H, s, CH), 3.77 (3 H, s, CH3), 3.64 (3 H, s, CH3), 2.17 (3 H, s, CH3). LCMS (15cm_Bicarb_GeminiNX_HPLC_MeCN) Rt 9.63 (min) m/z 375 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos; In 1,4-dioxane; at 90.0℃; for 6h;Inert atmosphere; | To a stirred solution of degassed dioxane (2 mL) was added 6-chloro-l -methyl- 1H- imidazo[4,5-c]pyridine (300 mg, 1.78 mmol), 7-amino-6-chloro-2H-benzo[6][l,4]oxazin-3(4H)-one (426 mg, 2.13 mmol), tris(dibenzylideneacetone)dipalladium(0) (81 mg, 0.089 mmol), 2- dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (170 mg, 0.356 mmol) and sodium teri-butoxide (258 mg, 2.67 mmol) and the resulting mixture was heated to 90C for 6 h. The reaction mixture was cooled to room temperature, filtered through a PL-Thiol MP SPE+ column (pre-conditioned with 1 mL MeOH) using MeOH (3 x 2 mL) to wash the column. The combined organics were concentrated in vacuo and the resulting residue was purified by preparative HPLC to give the desired compound. [00308] NMR delta (ppm)(DMSO-d6): 10.72 (1 H, s, NH), 8.57 (1 H, d, ArH), 8.14 (1 H, s, ArH), 8.06 (1 H, s, NH), 7.65 (1 H, s, ArH), 7.03 (1 H, d, ArH), 6.98 (1 H, s, ArH), 4.61 (2 H, s, CH2), 3.76 (3 H, s, CH3). [00309] LCMS (1 Ocm ESI Bicarb MeCN) tR 2.62 (min) m/z 330 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6-Chloro-l-methyl-lH-imidazo[4,5-c]pyridine (0.835 g, 5 mmol) was stirred with 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (0.29 g, 5 mmol), sodium fert-butoxide (0.73 g, 7.5 mol) and 7-amino-4-(4-methoxybenzyl)-2H-benzo[^][l,4]oxazin-3(4H)-one (1 .42 g, 5 mmol) in degassed dioxane (40 mL) under N2 (g) for 30 min. Tris(dibenzylideneacetone)dipalladium(0) (0.23 g, 0.25 mmol) was added and the reaction was stirred at 100 C for 5 h. The mixture was concentrated in vacuo and the residue was treated with water (50 mL) and extracted into EtOAc (2 x 200 mL). The combined extracts were washed with brine, dried (MgSO i), filtered and concentrated in vacuo to give the desired compound. For analytical purpose, a sample of this material (100 mg) was purified by preparative HPLC to give the desired compound. [00315] NMR delta (ppm)(DMSO-d6): 8.85 (1 H, s, NH), 8.55 (1 H, d, ArH), 8.08 (1 H, s, ArH), 7.43 (1 H, d, ArH), 7.23 (2 H, d, ArH), 7.09 (1 H, dd, ArH), 6.98-6.83 (3 H, m, ArH), 6.83 (1 H, d, ArH), 5.06 (2 H, s, CH2), 4.73 (2 H, s, CH2), 3.72 (6 H, d, CH3). [00316] LCMS (lOcm ESCI Bicarb MeCN) tR 3.16 (min) m/z 416 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In 1,4-dioxane; at 100.0℃; for 7h;Inert atmosphere; | A mixture of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.08 g), 6-chloro-l-methyl- lH-imidazo[4,5-c]pyridine (0.23 g, 0.0014 mol), 3-amino-4-ethyl-N,N-dimethylbenzamide (0.27 g, 0.0014 mol) and sodium tert-butoxide (0.20 g, 0.0021 mol) in 1,4-dioxane (15 mL) was stirred under N2 for 20 min. Tris(dibenzylideneacetone)dipalladium(0) (0.06 g) was added and the mixture was stirred at 100C for 7 h. The reaction mixture was concentrated in vacuo and the residue was treated with water and extracted into EtOAc. The organics were washed with brine, dried (MgSO i) and concentrated in vacuo to give the desired compound. For analytical purpose, a 60 mg sample was further purified by preparative HPLC to give the desired compound. [00324] NMR delta (ppm)(CHCl3-d): 8.69 (1 H, d, ArH), 7.71 (1 H, s, ArH), 7.52 (1 H, d, ArH), 7.32 (1 H, m, ArH), 7.16 (1 H, dd, ArH), 6.63 (1 H, d, ArH), 6.36 (1 H, s, NH), 3.68 (3 H, s, CH3), 3.09 (3 H, s, CH3), 3.03 (3 H, s, CH3), 2.69 (2 H, q, CH2), 1.24 (3 H, t, CH3). [00325] LCMS (lOcm ESCI Formic MeCN) tR 2.21 (min) m/z 324 (MH+). | |
With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In 1,4-dioxane; at 100.0℃; for 7h; | A mixture of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.08 g), 6-chloro-l-methyl- lH-imidazo[4,5-c]pyridine (0.23 g, 0.0014 mol), 3-amino-4-ethyl-N,N-dimethylbenzamide (0.27 g, 0.0014 mol) and sodium tert-butoxide (0.20 g, 0.0021 mol) in 1,4-dioxane (15 mL) was stirred under N2 for 20 min. Tris(dibenzylideneacetone)dipalladium(0) (0.06 g) was added and the mixture was stirred at 100C for 7 h. The reaction mixture was concentrated in vacuo and the residue was treated with water and extracted into EtOAc. The organics were washed with brine, dried (MgS04) and concentrated in vacuo to give the desired compound. NMR delta (ppm)(CHCl3-d): 8.69 (1 H, d, ArH), 7.71 (1 H, s, ArH), 7.52 (1 H, d, ArH), 7.32 (1 H, m, ArH), 7.16 (1 H, dd, ArH), 6.63 (1 H, d, ArH), 6.36 (1 H, s, NH), 3.68 (3 H, s, CH3), 3.09 (3 H, s, CH3), 3.03 (3 H, s, CH3), 2.69 (2 H, q, CH2), 1.24 (3 H, t, CH3). LCMS (lOcm ESCI Formic MeCN) Rt 2.21 (min) m/z 324 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dibenzylideneacetone bis(triphenylphiosphine) palladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In N,N-dimethyl-formamide; at 120.0℃; for 16h; | A mixture of 6-chloro-l-methyl-lH-imidazo[4,5-c]pyridine (intermediate 2) (84 mg, 0.5 mmol), 7-methyl-2,3-dihydrobenzo[6][l,4]dioxin-6-amine ( 1 .5 eq. ) , dib enzylidene ac etone bis(triphenylphiosphine) palladium (0) (5mol.%), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (10 mol.%), sodium tert-butoxide (1.5 eq.) and DMF (0.33 M) is stirred at 120 C for 16 h. The reaction mixture is allowed to cool to room temperature, filtered and the solvent removed in vacuo. The crude product is purified by preparative HPLC to afford the desired product. (4-ethyl-3-(l-methyl-lH-imidazo[4,5-c]pyridin-6-ylamino)phenyl)methanol was obtained by reacting (3-Amino-4-ethylphenyl)methanol with 6-chloro-l-methyl-lH-imidazo[4,5-c]pyridine according to method A" described above | |
With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In 1,4-dioxane; at 100.0℃; for 7h;Inert atmosphere; | To stirred degassed (N2) 1,4-dioxane (30 mL) was added (3-amino-4-ethylphenyl)MeOH (440 mg, 2.90 mmol), 6-chloro-l -methyl-lH-imidazo[4,5-c] pyridine (480 mg, 2.9 mmo l) , tris(dibenzylideneacetone)dipalladium(0) (0.12 mg, 0.145 mmol), 4,5-bis(diphenylphosphino)-9,9- dimethylxanthene (160 mg, 0.29 mmol) and sodium tert-butoxide (690 mg, 0.725 mmol). The reaction mixture was heated to 100 C for 7 h, cooled to room temperature, concentrated in vacuo and ethyl acetate and water were added. The ethyl acetate was separated, dried (MgSO i), filtered and concentrated in vacuo. The residue was dissolved in MeOH and loaded onto a 20 g SCX cartridge which was washed with MeOH and eluted with dilute ammonia in MeOH to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6-Chloro-l-methyl-lH-imidazo[4,5-c]pyridine (1.67 g, 0.01 mol), methyl 3-amino-4- ethylbenzoate (2.15 g, 0.012 mol) and caesium carbonate (4.56 g, 0.014 mol) were stirred together in tert-butanol (20 mL) under N2 for 20 min. Chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2'-4'-6'- tri-i-propyl-l,l'-biphenyl][2-(2-aminoethyl)phenyl] palladium(II) (BrettPhos Palladacycle) (0.079 g, 1 mol%) and 2-dicyclohexylphosphino-2',6'-di-iso-propoxy-l,l'-biphenyl (RuPhos) (0.046 g, 1 mol%) were added and the mixture was refluxed for 5 h. The reaction mixture was evaporated in vacuo and the residue was treated with water and extracted into EtOAc. The organics were dried (MgSO i) and concentrated in vacuo to give an oily solid. The residue was dissolved in methanol and loaded onto a 70 g SCX column which was washed with methanol (150 mL) before eluting the product with 7 N N in methanol : methanol (1 :4). The eluent was concentrated in vacuo and the residue was purified by flash chromatography (DCM to 5% methanol in DCM) to give the desired compound. [00338] NMR delta (ppm)(DMSO-d6): 8.51 (1 Eta, s, ArH), 8.16 (1 H, d, ArH), 8.07 (2 H, d, ArH, NH), 7.58 (1 H, dd, ArH), 7.35 (1 H, d, ArH), 6.83 (1 H, s, ArH), 3.96-3.72 (3 H, m, CH3), 3.72 (3 H, s, CH3), 2.71 (2 H, q, CH2), 1.17 (3 H, t, CH3). [00339] LCMS (1 Ocm ESCI Bicarb MeCN) tR 2.77 (min) m/z 311 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos; In 1,4-dioxane; at 100.0℃; for 1.5h;Inert atmosphere; | To stirred degassed (N2) 1,4-dioxane (230 mL) was added tert-butyl 4-(4-amino-3- ethylphenyl)-5,6-dihydropyridine-l(2H)-carboxylate (8.25 g, 27.3 mmol), 6-chloro-l -methyl- 1H- imidazo[4,5-c]pyridine (4.15 g, 24.8 mmol), tris(dibenzylideneacetone)dipalladium(0) (1.25 g, 1.37 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (1.30 g, 2.73 mmol) and sodium tert- butoxide (3.94 g, 30 mmol). The reaction mixture was heated to 100C for 1.5 h, cooled to room temperature, filtered through Celite and washed through with DCM. The filtrate was washed with water, dried (MgSO i), filtered and concentrated in vacuo and the resulting residue was purified by column chromatography using silica gel and eluting with 0-3%> MeOH in DCM. The fractions containing product were combined and concentrated in vacuo to give the desired compound. NMR delta (ppm)(DMSO-d6): 8.48 (1 H, d, NH), 8.04 (1 H, s, ArH), 7.89 (1 H, s, ArH), 7.56-7.49 (1 H, m, ArH), 7.30 (1 H, d, ArH), 7.23 (1 H, dd, ArH), 6.74-6.71 (1 H, m, ArH), 6.10 (1 H, s, CH), 4.00 (2 H, s, CH), 3.73-3.63 (3 H, m, CH3), 3.58-3.52 (2 H, m, CH), 2.70-2.59 (2 H, m, CH), 2.53-2.46 (2 H, s, CH), 1.55-1.35 (9 H, m, CH3), 1.18-1.09 (3 H, m, CH3). | |
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos; In 1,4-dioxane; at 100.0℃; for 1.5h;Inert atmosphere; | To stirred degassed (N2) 1,4-dioxane (230 mL) was added tert-butyl 4-(4-amino-3- ethylphenyl)-5,6-dihydropyridine-l(2H)-carboxylate (8.25 g, 27.3 mmol), 6-chloro-l -methyl- 1H- imidazo[4,5-c]pyridine (4.15 g, 24.8 mmol), tris(dibenzylideneacetone)dipalladium(0) (1.25 g, 1.37 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (1.30 g, 2.73 mmol) and sodium tert- butoxide (3.94 g, 30 mmol). The reaction mixture was heated to 100C for 1.5 h, cooled to room temperature, filtered through Celite and washed through with DCM. The filtrate was washed with water, dried (MgSO i), filtered and concentrated in vacuo and the resulting residue was purified by column chromatography using silica gel and eluting with 0-3% MeOH in DCM. The fractions containing product were combined and concentrated in vacuo to give the desired compound. NMR delta (ppm)(DMSO-d6): 8.48 (1 H, d, NH), 8.04 (1 H, s, ArH), 7.89 (1 H, s, ArH), 7.56-7.49 (1 H, m, ArH), 7.30 (1 H, d, ArH), 7.23 (1 H, dd, ArH), 6.74-6.71 (1 H, m, ArH), 6.10 (1 H, s, CH), 4.00 (2 H, s, CH), 3.73-3.63 (3 H, m, CH3), 3.58-3.52 (2 H, m, CH), 2.70-2.59 (2 H, m, CH), 2.53-2.46 (2 H, s, CH), 1.55-1.35 (9 H, m, CH3), 1.18-1.09 (3 H, m, CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In 1,4-dioxane; at 100.0℃; for 24h; | A stirred mixture of 4-ethyl-6-(thiophen-2-yl)pyridin-3-amine (0.15 g, 0.71 mmol), 6-chloro- 1 -methyl- lH-imidazo[4,5-c]pyridine (0.12 g, 0.71 mmol), sodium tert-butoxide ( 175 mg), tris(dibenzylideneacetone)dipalladium(0) (23 mg) and 2,2'-bis(diphenylphosphino)-l,l'-binaphthyl (22 mg) was heated in 1,4-dioxane (5 mL) at 100C in a sealed tube for 1 d. The mixture was evaporated in vacuo and the residue was partitioned between DCM and water. The organic phase was separated and the aqueous phase extracted with DCM (x 3), the combined organic phases were dried (MgSO i) and evaporated in vacuo. The residue was purified by flash chromatography (7N NH3 in methanol in DCM, 0-10%) to give the desired compound | |
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In 1,4-dioxane; at 100.0℃; for 24h;Sealed tube; | A stirred mixture of 4-ethyl-6-(thiophen-2-yl)pyridin-3-amine (0.15 g, 0.71 mmol), 6-chloro- 1 -methyl- lH-imidazo[4,5-c]pyridine (0.12 g, 0.71 mmol), sodium tert-butoxide ( 175 mg), tris(dibenzylideneacetone)dipalladium(0) (23 mg) and 2,2'-bis(diphenylphosphino)-l,l'-binaphthyl (22 mg) was heated in 1,4-dioxane (5 mL) at 100 C in a sealed tube for 1 d. The mixture was evaporated in vacuo and the residue was partitioned between DCM and water. The organic phase was separated and the aqueous phase extracted with DCM (x 3), the combined organic phases were dried (MgSO^ and evaporated in vacuo. The residue was purified by flash chromatography (7N NH3 solution in MeOH in DCM, 0-10%) to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 100.0℃; for 4h; | To a stirred solution of 6-Chloro-N-methyl-pyridine-3, 4-diamine (22 mmol) in trimethyl orthoformate (25 mL) was added formic acid (1 mL) and was heated at 100C for nearly 4 h when TLC showed the completion of reaction. The reaction was allowed to cool to room temperature and water (50 mL) was added and the mixture was extracted with ethyl acetate (4x50 mL), the combined organic layers were washed with aq. NaHCC>3 solution, dried over anhydrous sodium sulphate and concentration under reduced pressure gave the desired product Intermediate 2. H-NMR (400 MHz, DMSO-i: delta 3.84 (s, 3H), 7.83 (s, 1H), 8.39 (s, 1H), 8.74 (s, 1H). Mass (M+l): m/z 168. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos; In 1,4-dioxane; at 100℃; for 2h;Sealed tube; | 6-Chloro-l-methyl-lH-imidazo[4,5-c]pyridine (200 mg, 1.19 mmol), 2-chloro-N- methylaniline (185 mg, 1.31 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (57 mg, 0.12 mmol) and sodium tert-butoxide (172 mg, 1.79 mmol) were stirred in 1,4-dioxane (5 mL) and N2(g) was bubbled through the mixture for 10 min. Tris(dibenzylideneacetone)dipalladium(0) (54 mg, 0.06 mmol) was added and the dark mixture heated in a sealed tube at 100C for 2 h. The reaction mixture was cooled to room temperature and DCM and water were added. The aqueous phase was extracted with DCM and the combined organics filtered through a hydrophobic frit and then concentrated in vacuo. The residue was dissolved in DCM (5 mL) and passed through a PL-Thiol MP SPE+ column. DCM was passed through the column and the filtrate concentrated in vacuo. The residue was purified by preparative HPLC to give the desired compound. NuMuRhonu delta (ppm)(DMSO-d6): 8.47 (1 H, s, ArH), 8.02 (1 H, s, ArH), 7.59 (1 H, d, ArH), 7.47-7.38 (2 H, m, ArH), 7.39-7.31 (1 H, m, ArH), 6.39 (1 H, s, ArH), 3.66 (3 H, s, CH3), 3.35 (3 H, s , CH3). LCMS (lOcm ESCI Bicarb MeCN) Rt 3.22 (min) m/z 273 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos; In 1,4-dioxane; at 85.0℃; for 4h; | Methyl 4-amino-3-ethylbenzoate (0.9 g, 5.02 mmol), 6-chloro-l-methyl-lH-imidazo[4,5- c]pyridine (0.802 g, 4.788 mmol) and sodium tert-butoxide (0.689 g, 7.18 mmol) were suspended in 1,4- dioxane (40 mL). The reaction was stirred under an atmosphere of N2 (g) for 20 min then tris(dibenzylideneacetone)dipalladium(0) (219 mg, 0.23 mmol) and 2-dicyclohexylphosphino-2',4',6'- triisopropylbiphenyl (228 mg, 0.478 mmol) were added. The reaction was heated to 85C for 4 h then concentrated in vacuo. The crude material was dissolved in MeOH (40 mL) and HC1 (4 mL, 4 M in dioxane) and the reaction was refluxed for 4 h to re-esterify the hydrolysed ester. The reaction was concentrated in vacuo, diluted with EtOAc and washed with water then brine. The organic layer was dried (MgSO i), filtered and concentrated in vacuo. The residue was purified by column chromatography using silica gel and eluting with DCM:MeOH 97:3 to give the desired compound |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos; In 1,4-dioxane; at 100.0℃; for 24h;Inert atmosphere; | To stirred degassed (N2) 1,4-dioxane (10 mL) was added 2-ethyl-4-(l-methyl-lH-pyrazol-4- yl)aniline (400 mg, 2.00 mmol), 6-chloro-l-methyl-lH-imidazo[4,5-c]pyridine (303 mg, 1.8 mmol), tris(dibenzylideneacetone)dipalladium(0) (82 mg, 0.09 mmol), 2-dicyclohexylphosphino-2',4',6'- triisopropylbiphenyl (86 mg, 0.18 mmol) and sodium tert-butoxide (260 mg, 2.7 mmol). The reaction mixture was heated to 100C for 1 d, cooled to room temperature, filtered through Celite and washed through with DCM. The reaction mixture was washed with water and the layers were separated and the aqueous layer further extracted with DCM. The organics were combined, dried (hydrophobic filter) and concentrated in vacuo and the resulting residue was purified by column chromatography using silica gel and eluting with 0-5% MeOH in DCM. The fractions containing product were combined and concentrated in vacuo to give the desired compound. NMR delta (ppm)(DMSO-d6): 8.47 (1 H, s, NH), 8.07 (1 H, s, ArH), 8.02 (1 H, s, ArH), 7.89-7.76 (2 H, m, ArH), 7.48-7.40 (2 H, m, ArH), 7.37-7.33 (1 H, m, ArH), 6.64 (1 H, s, ArH), 3.87 (3 H, s, CH3), 3.67 (3 H, s, CH3), 2.70-2.60 (2 H, m, CH2), 1.20-1.11 (3 H, m, CH3). LCMS (lOcm ESCI Bicarb MeCN) Rt 2.67 (min) m/z 333 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos; In 1,4-dioxane; at 100.0℃; for 24h;Inert atmosphere; | General procedure: To stirred degassed (N2) 1,4-dioxane (10 mL) is added the product of step i) above (2.00 mmol), 6-chloro-l -methyl- lH-imidazo[4,5-c]p y r i d i n e ( 3 0 3 m g , 1 . 8 m m o l ) , tris(dibenzylideneacetone)dipalladium(0) (82 mg, 0.09 mmol), 2-dicyclohexylphosphino-2',4',6'- triisopropylbiphenyl (86 mg, 0.18 mmol) and sodium tert-butoxide (260 mg, 2.7 mmol). The reaction mixture is heated to 100C for 1 d, cooled to room temperature, filtered through Celite and washed through with DCM. The reaction mixture is washed with water and the layers are separated and the aqueous layer further extracted with DCM. The organics are combined, dried (hydrophobic filter) and concentrated in vacuo and the resulting residue is purified by column chromatography using silica gel. The fractions containing product are combined and concentrated in vacuo to give the desired compound |
A256224 [2589-11-9]
6-Chloro-1H-imidazo[4,5-c]pyridine
Similarity: 0.94
A100287 [52559-17-8]
6-Chloro-3H-imidazo[4,5-c]pyridin-4-amine
Similarity: 0.79
A130659 [50432-68-3]
4-Chloro-1-methyl-1H-imidazo[4,5-c]pyridine
Similarity: 0.73
A224754 [887147-19-5]
4,6-Dichloro-1-methyl-1H-imidazo[4,5-c]pyridine
Similarity: 0.72
A256224 [2589-11-9]
6-Chloro-1H-imidazo[4,5-c]pyridine
Similarity: 0.94
A100287 [52559-17-8]
6-Chloro-3H-imidazo[4,5-c]pyridin-4-amine
Similarity: 0.79
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