Home Cart 0 Sign in  
X

[ CAS No. 82261-42-5 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 82261-42-5
Chemical Structure| 82261-42-5
Chemical Structure| 82261-42-5
Structure of 82261-42-5 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 82261-42-5 ]

Related Doc. of [ 82261-42-5 ]

Alternatived Products of [ 82261-42-5 ]

Product Details of [ 82261-42-5 ]

CAS No. :82261-42-5 MDL No. :MFCD00956763
Formula : C11H10N2 Boiling Point : -
Linear Structure Formula :- InChI Key :DKFDPLVNPGJNDE-UHFFFAOYSA-N
M.W :170.21 Pubchem ID :459522
Synonyms :

Calculated chemistry of [ 82261-42-5 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 12
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 54.08
TPSA : 38.91 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.06 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.58
Log Po/w (XLOGP3) : 1.8
Log Po/w (WLOGP) : 2.34
Log Po/w (MLOGP) : 1.47
Log Po/w (SILICOS-IT) : 2.31
Consensus Log Po/w : 1.9

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.65
Solubility : 0.384 mg/ml ; 0.00226 mol/l
Class : Soluble
Log S (Ali) : -2.24
Solubility : 0.988 mg/ml ; 0.00581 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.18
Solubility : 0.0113 mg/ml ; 0.0000665 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.65

Safety of [ 82261-42-5 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302+H312+H332-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 82261-42-5 ]

* 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.

  • Downstream synthetic route of [ 82261-42-5 ]

[ 82261-42-5 ] Synthesis Path-Downstream   1~79

  • 1
  • [ 82261-42-5 ]
  • [ 3460-49-9 ]
  • <i>N</i>-(4-ethoxy-phenyl)-<i>N</i>'-(4-[3]pyridyl-phenyl)-thiourea [ No CAS ]
YieldReaction ConditionsOperation in experiment
With ethanol
  • 2
  • [ 82261-42-5 ]
  • [ 50785-45-0 ]
  • [ 113182-91-5 ]
YieldReaction ConditionsOperation in experiment
With ethanol
  • 3
  • [ 82261-42-5 ]
  • [ 3460-50-2 ]
  • [ 124138-25-6 ]
YieldReaction ConditionsOperation in experiment
With ethanol
  • 4
  • [ 82261-42-5 ]
  • [ 17608-15-0 ]
  • <i>N</i>-(4-pentyloxy-phenyl)-<i>N</i>'-(4-[3]pyridyl-phenyl)-thiourea [ No CAS ]
YieldReaction ConditionsOperation in experiment
With ethanol
  • 5
  • [ 4282-46-6 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
97% With palladium on activated charcoal; hydrogen In methanol at 20℃; 2 4-(Pyridin-3-yl)aniline (3) To a solution of 2 (920 mg, 4.6 mmol) in methanol (20 mL) was added Pd/C (90 mg), and the reaction mixture was stirred at room temperature under H2 overnight. The mixture was filtered, and the filtrate was concentrated to give the desired product (740 mg, 97%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.79 (d, J = 2.0 Hz, 1H), 8.50 (dd, J = 4.8, 1.2 Hz, 1H), 7.84-7.76 (m, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.31 (dd, J = 8.0, 4.8 Hz, 1H), 6.78 (d, J = 8.4 Hz, 2H), 3.81 (s, 2H).
95% In dichloromethane 6 3-(4-Aminophenyl)pyridine (structure 3, where R1 =3-pyridyl) 3-(4-Aminophenyl)pyridine (structure 3, where R1 =3-pyridyl) In a flame-dried r.b. flask equipped with a magnetic stirring bar was dissolved 3-(4-nitrophenyl)pyridine (131 mg, 0.655 mmol) and 10% Pd on C (10 mg) in anhydrous CH2 Cl2 (3 mL) was added. The flask was repeatedly evacuated and filled with N2 to remove any residual O2, and then H2 gas was introduced. The solution was stirred at rt for 18 h, filtered though a Celite plug and concentrated in vacuo to give the desired amine (105 mg, 95%) as an off-white solid.
91% With iron; ammonium chloride In ethanol; water at 70 - 80℃; for 1h; 123.ii (ii) 4-(Pyridine-3-yl)aniline anol(50 ml) and water (10 ml) was mixed and added with iron powder. The mixture was heated to 70-80°C. Ammonium chloride (0.261 g, 5 mmol) was added to the mixture, and then 3-(4-nitrophenyl)pyridine(2.0 g, 10.0 mmol) obtained in (i) was added. The reaction was carried out at 70-80°C for 1 hour. After the completion of the reaction, the iron powder was filtered while hot through Celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in isopropyl alcohol, crystallized and filtered with addition of water to give the title compound (3.0 g, 91.0%).
70% With hydrogenchloride; iron In 1,4-dioxane; water for 5h; Reflux; 4.2 2) Preparation of 3-(4-aminophenyl)pyridine Iron powder 1.56 g (0.03 mol) of water (2 mL) and dioxane (10 mL) were placed in a 50 mL three-necked flask.Add hydrochloric acid (0.5 mL) and warm to 50 ° C and stir for half an hour, then add 3-(4-nitrophenyl)pyridine 1.6 g (0.008 mol),The temperature was refluxed for 5 hours, the reaction was completed by TLC, the reaction was stopped, filtered, and the mother liquid was concentrated to dryness.Ethyl acetate (5 mL) was added to the residue, and the mixture was evaporated to reflux.Solid dried to a white solid 0.93 g (70%)
With hydrogenchloride; tin
With hydrogenchloride; hydrogen In methanol
With sodium dithionite; water In methanol for 3h; Heating / reflux; 10.2 [0353] Experimental Details: A mixture of compound 3 (2 g, 0.1 mol) and Na2S2O4 (5.2 g, 0.3 mol) in methanol (80 mL) and H2O (20 mL) was heated to reflux for 3 h. The reaction was concentrated to dryness under reduced pressure. The residue was dissolved into water and then was extracted with EA (150 mL). The organic layer was washed with brine twice and dried over Na2SO4. After filtrating off the Na2SO4, the filtrate was concentrated to give the product 4.
With sodium dithionite In methanol; water for 3h; Heating; Reflux; 8.2 Experimental Details: A mixture of compound 3 (2 g, 0.1 mol) and Na2S2O4 (5.2 g, 0.3 mol) in methanol (80 mL) and H2O (20 mL) was heated to reflux for 3 h. The reaction was concentrated to dryness under reduced pressure. The residue was dissolved into water and then was extracted with EA (150 mL). The organic layer was washed with brine twice and dried over Na2SO4. After filtrating off the Na2SO4, the filtrate was concentrated to give the product 4.
With palladium 10% on activated carbon; hydrogen In methanol; ethyl acetate for 5h; 29 A mixture of 3-(4-nitrophenyl)pyridine (487 mg, 2.43 mmol) and Pd-C (10%, 80 mg) in MeOH (25 mL) and EtOAc (5 mL) was hydrogenated under balloon H2 for 5 h. The mixture was then filtered through celite. The filtrate was concentrated in vacuo to give 4-(pyridin-3-yl)aniline as a solid (403 mg).
With iron; ammonium chloride In ethanol; water at 85℃; for 1h; 12 The above product, reduced iron powder (3eq) and ammonium chloride (3eq) were placed in a mixed solvent of 10ml of ethanol and water (1: 1), and reacted at 85 ° C for 1h.After filtration, the filter cake was washed with ethyl acetate, separated, washed with saturated brine, and dried over anhydrous sodium sulfate.The organic solvent was distilled off under reduced pressure, and a yellow solid was separated by column chromatography, with a yield of 92.4%.

  • 6
  • [ 82261-42-5 ]
  • [ 108-24-7 ]
  • [ 154164-35-9 ]
YieldReaction ConditionsOperation in experiment
78% In toluene at 20℃; for 12h; 4.3 3) Preparation of 3-(4-acetamidophenyl)pyridine 3-(4-aminophenyl)pyridine 1 g (0.006 mol) of acetic anhydride (0.5 mL) and toluene (5 mL) were added to a 50 ml three-necked flask, and the mixture was stirred at room temperature for 12 hours.TLC followed the completion of the reaction, poured into water, washed with alkaline sodium carbonate solution to alkaline, and allowed to stand for separation. The organic layer was washed with saturated brine.Dry and concentrate to give a solid 0.97 g (78%).No purification is required for the next step.
With triethylamine In dichloromethane Ambient temperature; Yield given;
  • 7
  • [ 82261-42-5 ]
  • [ 68223-13-2 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; water; sodium nitrite 1.) water, 1 h, 2.) 160 deg C, 10 min; Yield given. Multistep reaction;
22 4-(3-Pyridyl)phenol PREPARATION 22 4-(3-Pyridyl)phenol Refer to Chart B (conversion of XXII to XXIII). Using the procedure described above, 3-(4'-aminophenyl)pyridine (10.0 g, 0.059 mol) is converted to the phenol. A total of 7.66 g of product is obtained, after chromatography, which is then recrystallized from acetone-hexane to give 6.52 g (65% of theory) of off-white crystals which have as melting point of 202°-203° C. The C:H:N ratio is 76.71:5.42:8.13; when repeated, it is 76.76:5.30:8.18. The IR (mull) spectrum reveals peaks at 2688, 2652, 2624, 2455, 1608, 1595, 1583, 1525, 1292, 1274, 1251, 1180, 842, 830, and 812 cm-1.
  • 8
  • [ 82261-42-5 ]
  • [ 100-97-0 ]
  • 2,8-Di(pyridin-3-yl)-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine [ No CAS ]
YieldReaction ConditionsOperation in experiment
26% With trifluoroacetic acid Ambient temperature;
  • 9
  • [ 82261-44-7 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
92% With sodium hydroxide In various solvent(s) for 1.5h; Heating;
  • 10
  • [ 82261-42-5 ]
  • [ 215527-54-1 ]
YieldReaction ConditionsOperation in experiment
88% With benzyltrimethylammonium tribromide; calcium carbonate In methanol; dichloromethane at 20℃; for 3h;
76.2% With bromine In acetonitrile at 20℃; for 1h; 128.i (i) 2,6-Dibromo-4-(pyridine-3-yl)aniline 3-(4'-Aminophenyl)pyridine (1.5 g, 9mmol) was dissolved in acetonitrile (15ml), and added dropwise with bromine (2.88 g, 18mmol). The mixture was reacted at room temperature for 1 hour, added with water and neutralized with aqueous sodium hydroxide. The solvent was distilled off under reduced pressure. The precipitated crystals were filtered to give the title compound (2.3 g, 76.2%).
  • 11
  • [ 89878-14-8 ]
  • [ 106-40-1 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
68% With potassium hydroxide; tetrabutylammomium bromide In tetrahydrofuran for 24h; Heating;
With potassium hydroxide; tetrabutylammomium bromide In tetrahydrofuran; water; ethyl acetate for 14h; Heating / reflux; 14 4-(Pyridin-3-yl)phenylamine Reference Example 14 4-(Pyridin-3-yl)phenylamine Under argon atmosphere, 3-pyridyl-diethyl borane (1.5 g) and water (1 drop) were added to a THF solution (60 ml) of 4-aminobromobenzene (855 mg), tetrakistriphenylphosphine palladium (672 mg), tetrabutylammonium bromide (937 mg) and potassium hydroxide (979 mg), followed by heating under reflux for 14 hours. After concentration of the reaction solution, the mixture was diluted with ethyl acetate (300 ml) and washed twice with water (100 ml). After drying over anhydrous sodium sulfate, the solvent was evaporated, and the residue was purified by flash silica gel column chromatography (hexane:ethyl acetate = 1:1 to ethyl acetate) to obtain the title compound (465 mg) as a white solid. 1H-NMR (400 MHz, CDCl3) δ: 3.79 (2H, br s), 6.77 (2H, d, J=6.6 Hz), 7.30 (1H, dd, J=4.9 and 7.8 Hz), 7.40 (2H, d, J=6.6 Hz), 7.80 (1H, dd, J=3.9 Hz, 7.9 Hz), 8.50 (1H, d; J=4.7 Hz), 8.79 (1H, s). FAB-MS m/z: 171 (M+H)+.
  • 14
  • [ 626-55-1 ]
  • [ 33976-43-1 ]
  • [ 82261-42-5 ]
  • 15
  • [ 82261-42-5 ]
  • [ 215527-55-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 88 percent / benzyltrimethylammonium tribromide; CaCO3 / CH2Cl2; methanol / 3 h / 20 °C 2: 57 percent / Na2CO3 / Pd(PPh3)4 / benzene; ethanol; H2O / 24 h / Heating
  • 16
  • [ 82261-42-5 ]
  • N-[(4-nitrophenyl)thio]-2,6-diphenyl-4-(3-pyridyl)phenylaminyl [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 88 percent / benzyltrimethylammonium tribromide; CaCO3 / CH2Cl2; methanol / 3 h / 20 °C 2: 57 percent / Na2CO3 / Pd(PPh3)4 / benzene; ethanol; H2O / 24 h / Heating 3: 80 percent / Et3N / tetrahydrofuran / 2 h / 0 °C 4: 19 percent / K2CO3; PbO2 / benzene / 0.05 h
  • 17
  • [ 82261-42-5 ]
  • [ 215527-56-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 88 percent / benzyltrimethylammonium tribromide; CaCO3 / CH2Cl2; methanol / 3 h / 20 °C 2: 57 percent / Na2CO3 / Pd(PPh3)4 / benzene; ethanol; H2O / 24 h / Heating 3: 80 percent / Et3N / tetrahydrofuran / 2 h / 0 °C
  • 18
  • [ 82261-42-5 ]
  • N-[(2,4-dichlorophenyl)thio]-2,6-diphenyl-4-(3-pyridyl)phenylaminyl [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 88 percent / benzyltrimethylammonium tribromide; CaCO3 / CH2Cl2; methanol / 3 h / 20 °C 2: 57 percent / Na2CO3 / Pd(PPh3)4 / benzene; ethanol; H2O / 24 h / Heating 3: 69 percent / Et3N / tetrahydrofuran / 2 h / 0 °C 4: 25 percent / K2CO3; PbO2 / benzene / 0.05 h
  • 19
  • [ 82261-42-5 ]
  • [ 215527-57-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 88 percent / benzyltrimethylammonium tribromide; CaCO3 / CH2Cl2; methanol / 3 h / 20 °C 2: 57 percent / Na2CO3 / Pd(PPh3)4 / benzene; ethanol; H2O / 24 h / Heating 3: 69 percent / Et3N / tetrahydrofuran / 2 h / 0 °C
  • 20
  • [ 82261-42-5 ]
  • [ 215527-69-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 88 percent / benzyltrimethylammonium tribromide; CaCO3 / CH2Cl2; methanol / 3 h / 20 °C 2: 45 percent / Na2CO3 / Pd(PPh3)4 / benzene; ethanol; H2O / 24 h / Heating
  • 21
  • [ 82261-42-5 ]
  • N-[(2,4-dichlorophenyl)thio]-2,6-di(phenyl-d5)-4-(3-pyridyl)aniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 88 percent / benzyltrimethylammonium tribromide; CaCO3 / CH2Cl2; methanol / 3 h / 20 °C 2: 45 percent / Na2CO3 / Pd(PPh3)4 / benzene; ethanol; H2O / 24 h / Heating 3: 65 percent / Et3N / tetrahydrofuran / 2 h / 0 °C
  • 22
  • [ 1008-88-4 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 54 percent / HNO3, H2SO4 / 1 h / 0 °C 2: H2, HCl / Pd/C / methanol / 760 Torr
Multi-step reaction with 2 steps 1: concentrated sulfuric acid / 100 °C 2: tin; concentrated hydrochloric acid
Multi-step reaction with 2 steps 1: sulfuric acid; nitric acid / water / 1 h 2: iron; ammonium chloride / water; ethanol / 1 h / 70 - 80 °C
  • 23
  • [ 82261-42-5 ]
  • [ 445012-62-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 71 percent / HNO3, H2SO4 / 1 h / Ambient temperature 3: aq. HCl / 1 h / Heating 4: H2, HCl / 10percent Pd/C / methanol / 760 Torr
  • 24
  • [ 82261-42-5 ]
  • [ 167959-19-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 71 percent / HNO3, H2SO4 / 1 h / Ambient temperature 3: aq. HCl / 1 h / Heating
  • 25
  • [ 82261-42-5 ]
  • [ 154164-36-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 71 percent / HNO3, H2SO4 / 1 h / Ambient temperature
  • 26
  • [ 82261-42-5 ]
  • 6-(3-pyridyl)-2,3(1H,4H)-quinoxalinedione hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: Et3N / CH2Cl2 / Ambient temperature 2: 71 percent / HNO3, H2SO4 / 1 h / Ambient temperature 3: aq. HCl / 1 h / Heating 4: H2, HCl / 10percent Pd/C / methanol / 760 Torr 5: 4N aq. HCl
  • 27
  • [ 82261-42-5 ]
  • [ 85633-41-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1.) NaNO2, conc H2SO4, 2.) H2O / 1.) water, 1 h, 2.) 160 deg C, 10 min 2: 1.) trifluoroacetic acid, 2.) water / 1.) 80 deg C, 4 h, 2.) RT, 20 min
  • 28
  • [ 82261-42-5 ]
  • [ 85633-42-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 1.) NaNO2, conc H2SO4, 2.) H2O / 1.) water, 1 h, 2.) 160 deg C, 10 min 2: 1.) trifluoroacetic acid, 2.) water / 1.) 80 deg C, 4 h, 2.) RT, 20 min 3: 61 percent / NaH, dicyclohexyl-18-crown-6 / toluene / 48 h / Ambient temperature
  • 29
  • [ 82261-42-5 ]
  • [ 85633-43-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 1.) NaNO2, conc H2SO4, 2.) H2O / 1.) water, 1 h, 2.) 160 deg C, 10 min 2: 1.) trifluoroacetic acid, 2.) water / 1.) 80 deg C, 4 h, 2.) RT, 20 min 3: 61 percent / NaH, dicyclohexyl-18-crown-6 / toluene / 48 h / Ambient temperature 4: 0.1N aq. NaOH / methanol / 1.5 h
  • 30
  • [ 110-86-1 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 72 percent / H2O / 40 h / Irradiation; Corex filter 2: 92 percent / NaOH / various solvent(s) / 1.5 h / Heating
Multi-step reaction with 2 steps 1: 83 percent Chromat. / H2O / 40 h / Irradiation 2: 92 percent / NaOH / various solvent(s) / 1.5 h / Heating
  • 31
  • [ 82261-42-5 ]
  • (4-[3]pyridyl-phenyl)-hydrazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-pyridin-3-ylaniline With hydrogenchloride; sodium nitrite In water at 0℃; for 1.5h; Stage #2: With hydrogenchloride; tin(ll) chloride In water at 20℃; for 1h; Stage #3: With potassium hydroxide In water 15 4-(Pyridin-3-yl)phenylhydrazine Reference Example 15 4-(Pyridin-3-yl)phenylhydrazine 4-(Pyridin-3-yl)phenylamine (214 mg) was dissolved in hydrochloric acid (4 ml) and water (2 ml), and an aqueous solution (2 ml) of sodium nitrite (95 mg) was added dropwise to the solution over 30 minutes at 0°C. After stirring at the same temperature for 1 hour, a hydrochloric acid solution (2 ml) of tin(II) chloride dihydrate (709 mg) was added to the mixture, followed by stirring at room temperature for 1 hour. The reaction solution was alkalified by adding an aqueous solution of 20 wt% potassium hydroxide and extracted with chloroform: methanol = 9:1 (100 ml). After drying over anhydrous sodium sulfate, the solvent was evaporated, and the thus obtained solid was washed with diethyl ether to obtain the title compound (183 mg) as a pale yellow solid. 1H-NMR (400 MHz, CDCl3) δ: 3.64 (2H, br s), 5.31 (1H, br s), 6.93 (2H, d, J=8.9 Hz), 7.31 (1H, dd, J=4.9 Hz, 7.8 Hz), 7.48 (2H, d, J=8.8 Hz), 7.82 (1H, dd, J=1.7 Hz, 7.9 Hz), 8. 51 (1H, dd, J=1.5 Hz, 4.9 Hz), 8.81 (1H, d, J=2.4 Hz). ESI-MS m/z: 186 (M+H)+
  • 32
  • [ 82261-42-5 ]
  • [ 79-37-8 ]
  • [ 229006-96-6 ]
  • N-[4-(pyridin-3-yl)phenyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In tetrahydrofuran; water; N,N-dimethyl-formamide W.164 WORKING EXAMPLE 164 (Production of Compound 164) WORKING EXAMPLE 164 (Production of Compound 164) Under nitrogen atmosphere, oxalyl chloride (0.28 ml) was added to a solution of 7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.60 g) in tetrahydrofuran (10 ml) at room temperature. To the mixture was added a drop of DMF, and the mixture was stirred for 1 hour. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in tetrahydrofuran (10 ml). To the solution were added triethylamine (0.60 ml) and 3-(4-aminophenyl)pyridine (J. Chem. Soc., p.1511, 1960) (0.40 g) at 0° C., and the mixture was stirred at room temperature for 2 hours. The reaction mixture was added to vigorously stirred water to stop the reaction. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate, concentrated and recrystallized from ethanol to give N-[4-(3-pyridyl)phenyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 164) (750 mg) as yellow crystals. m.p. 214-216° C.; 1 H-NMR (200 MHz, CDCl3) δ 2.39 (3H, s), 3.07-3.11 (2H, m), 4.34-4.39 (2H, m), 7.06 (1H, d, J=8.2 Hz), 7.18-7.63 (10H, m), 7.71-7.90 (4H, m), 8.57-8.59 (1H, m), 8.85 (1H, d, J=1.8 Hz). IR (KBr) 3313, 1666, 1524, 1493, 1321, 1244, 808 cm-1; Elemental Analysis for C29 H24 N2 O2.0.2H2 O; Calcd. C, 79.87; H, 5.64; N, 6.42: Found. C, 80.00; H, 5.59; N, 6.00.
  • 33
  • [ 82261-42-5 ]
  • [ 79-37-8 ]
  • [ 229006-67-1 ]
  • (E)-N-[4-(pyridin-3-yl)phenyl]-3-(4-methylphenyl)cinnamamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In tetrahydrofuran; water; N,N-dimethyl-formamide W.192 WORKING EXAMPLE 192 (Production of Compound 192) WORKING EXAMPLE 192 (Production of Compound 192) Under nitrogen atmosphere, oxalyl chloride (0.27 ml) was added to a solution of (E)-3-(4-methylphenyl)cinnamic acid (0.50 g) in tetrahydrofuran (10 ml) at room temperature. To the mixture was added a drop of DMF, and the mixture was stirred for 1 hour. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in tetrahydrofuran (10 ml). To the solution were added triethylamine (0.60 ml) and 3-(4-aminophenyl)pyridine (0.39 g) at 0° C., and the mixture was stirred at room temperature for 18 hours. The reaction mixture was added to vigorously stirred water to stop the reaction. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated. The residue was purified with column chromatography (ethyl acetate) to give yellow crystals, which were recrystallized from tetra-hydrofuran-ethanol to give (E)-N-[4-(3-pyridyl)phenyl]-3-(4-methylphenyl)cinnamamide (Compound 192) (447 mg) as pale yellow crystals. m.p. 213-214° C.; 1 H-NMR (200 MHz, CDCl3) δ 2.15 (3H, s), 6.65 (1H, d, J=15.4 Hz), 7.26-7.64 (11H, m), 7.75-7.90 (5H, m), 8.59 (1H, dd, J=4.8, 1.8 Hz), 8.85 (1H, d, J=1.8 Hz). IR (KBr) 3344, 1660, 1626, 1525, 1481, 1335, 1171, 978, 795 cm-1; Elemental Analysis for C27 H22 N2 O; Calcd. C, 83.05; H, 5.68; N, 7.17: Found. C, 83.01; H, 5.82; N, 7.23.
  • 34
  • [ 82261-42-5 ]
  • [ 179894-41-8 ]
YieldReaction ConditionsOperation in experiment
0.3% 6 3-(4-Aminophenyl)pyridine (structure 3, where R1 =3-pyridyl) 1,2-Dihydro-2,2,4-trimethyl-6-(3-pyridyl)quinoline (Compound 105, structure 4, where R1 =3-pyridyl) This compound was prepared using the procedure of EXAMPLE 2 from 3-(4-aminophenyl)pyridine (105 mg, 0.62 mmol) to afford Compound 105 (0.5 mg, 0.3%) as an off-white solid. Data for Compound 105: Rf =0.44 (silica gel, hexane/EtOAc, 3:1); 1 H NMR (400 MHz, CDCl3) 9.13 (s, 1H), 8.58 (d, J=2.5, 1H), 7.48 (m, 1H), 7.36 (s, 1H), 7.26 (s, 1H), 6.96 (s, 1H), 6.82 (m, 1H), 6.26 (d, J=4.0, 1H), 5.12 (s, 1H), 1.80 (s, 3H), 1.06 (s, 6H).
0.3% 6 1,2-Dihydro-2,2,4-trimethyl-6-(3-pyridyl)quinoline (Compound 105, structure 4 of Scheme I, where R1 =3-pyridyl) 1,2-Dihydro-2,2,4-trimethyl-6-(3-pyridyl)quinoline (Compound 105, structure 4, where R1 =3-pyridyl): This compound was prepared using the procedure of EXAMPLE 2 from 3-(4-aminophenyl)pyridine (105 mg, 0.62 mmol) to afford Compound 105 (0.5 mg, 0.3%) as an off-white solid. Data for Compound 105: Rf =0.44 (silica gel, hexane/EtOAc, 3:1); 1 H NMR (400 MHz, CDCl3) 9.13 (s, 1H), 8.58 (d, J=2.5, 1H), 7.48 (m, 1H), 7.36 (s, 1H), 7.26 (s, 1H), 6.96 (s, 1H), 6.82 (m, 1H), 6.26 (d, J=4.0, 1H), 5.12 (s, 1H), 1.80 (s, 3H) 1.06 (S, 6H).
  • 35
  • [ 82261-42-5 ]
  • [ 79-37-8 ]
  • [ 120553-24-4 ]
  • (E)-5,5-bis-(4-methoxyphenyl)-N-[4-(3-pyridinyl)phenyl]-2,4-pentadienamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane; toluene 288 Preparation of (E)-5,5-bis(4-methoxyphenyl)-N-[4-(3-pyridinyl) phenyl-2,4-pentadienamide EXAMPLE 288 Preparation of (E)-5,5-bis(4-methoxyphenyl)-N-[4-(3-pyridinyl) phenyl-2,4-pentadienamide Oxalyl chloride (0.5 mL) was added to a suspension of (E)-5.5-bis(4-methoxyphenyl)-2,4-pentadienoic acid (0.776 g) in toluene (5 mL) and the mixture was stirred at room temperature for 30 minutes. After the solvent was removed under reduced pressure, the acid chloride was dissolved in dichloromethane (10 mL) and added dropwise to a stirred solution of 3-(4-aminophenyl)pyridine (0.426 g) and triethylamine (0.87 mL) in dichloromethane (20 mL) at 5° C. The reaction was allowed to proceed overnight at room temperature, then was washed with 0.5N NaOH solution and with brine. Evaporation of the dried (Na2 SO4) organic layer gave a foam which was crystallized from acetone-ethyl acetate to yield 0.7 g of (E)-5,5-bis-(4-methoxyphenyl)-N-[4-(3-pyridinyl)phenyl]-2,4-pentadienamide, mp 210°-212° C. Anal. Calcd for C30 H26 N2 O3: C, 77.90; H 5.67; N, 6.06 Found: C, 77.85; H, 5.91, N, 5.94
  • 36
  • [ 82261-42-5 ]
  • [ 29950-12-7 ]
  • 3-amino-4-[4-(pyridin-3-yl)anilino]-3-cyclobutene-1,2-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
In pyridine; <i>N</i>-methyl-acetamide; water 1 3-Amino-4-[4-(3-Pyridyl)Anilino]-3-Cyclobutene-1,2-Dione EXAMPLE 1 3-Amino-4-[4-(3-Pyridyl)Anilino]-3-Cyclobutene-1,2-Dione A solution of 3-(4-aminophenyl)pyridine (0.51 g) and 3-amino-4-ethoxy-3-cyclobutene 1,2-dione (0.42 g) in pyridine (2 ml) is stirred at 80° for 20 hours. The cool mixture is treated with water (15 ml), and the solid filtered off and washed with water and hot methanol. Recrystallation from dimethylformamide gives 0.33 g of the title compound, mp 3224° C. dec.
  • 37
  • [ 82261-42-5 ]
  • [ 1044209-33-7 ]
  • [ 1044209-37-1 ]
YieldReaction ConditionsOperation in experiment
With sodium t-butanolate In toluene at 80℃; for 48h; 10.3 [0355] Experimental Details: To a stirred and degassed mixture of compound 5 (228 mg, 88 mmol) and compound 4 (150 mg, 88 mmol), and tBuONa (170 mg, 176 mmol) and BINAP (210 mg, 176 mmol) in toluene (25 mL) was added Pd2(dba)3 (79 mg, 0.88 mmol) under N2 atmosphere and stirred at 80 °C for 48 h. After filtering off the solid, the filtrate was concentrated to give the crude product 6.
With sodium t-butanolate In toluene at 80℃; for 48h; Inert atmosphere; 8.3 Experimental Details: To a stirred and degassed mixture of compound 5 (228 mg, 88 mmol) and compound 4 (150 mg, 88 mmol), and tBuONa (170 mg, 176 mmol) and BINAP (210 mg, 176 mmol) in toluene (25 mL) was added Pd2(dba)3 (79 mg, 0.88 mmol) under N2 atmosphere and stirred at 80° C. for 48 h. After filtering off the solid, the filtrate was concentrated to give the crude product 6.
  • 38
  • [ 1692-25-7 ]
  • [ 106-40-1 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
99% With potassium phosphate; palladium dichloride; S-2,2',6,6'-tetramethoxy-4,4'-bis(diphenylphosphino)-3,3'-bipyridine In butan-1-ol at 100℃; for 20h; Inert atmosphere;
85% With potassium phosphate tribasic heptahydrate In 1,4-dioxane for 48h; Reflux;
85% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In water at 100℃; for 18h; Inert atmosphere;
71% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water for 3.5h; Inert atmosphere; 12 Example 12 Preparation of 4-(3-pyridyl)-phenylamine (Intermediate 11) 4-Bromo-aniline 827 mg (4.81 mmol) and 3-boric acid pyridine 519 mg (4.81 mmol. 1 eq) potassium carbonate(3.99 g 24.88 mmol 6 eq) [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (351.35 mg 481 mmol 6 eq) was placed in a 100 ml two-necked flask and infused with 30 ml (dioxane: water) =3:1) Nitrogen protection, 80 for 3.5 h. After the TLC monitoring reaction is completed, the post-treatment distillation is carried out under reduced pressure to about 10 ml, and the solution is poured into a separating funnel, extracted with dichloromethane for 2-3 times, dried over anhydrous Na 2 SO 4 , filtered, and evaporated to dryness to give a black oily drop. Separation and purification with petroleum ether: ethyl acetate = 6:1 silica gel column chromatography to give a pale yellow oily liquid about 580 mg, yield 71%.
71% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 110℃; for 16h; Inert atmosphere; 40 Example 40: 4-(Pyridin-3-yl)aniline (40.2) [00499] K2CO3 (3.24 g, 23.48 mmol) and [l,r-bis(diphenylphosphino)ferrocene] palladium(II) dichloride (0.22 g, 0.29 mmol) were added to a stirred solution of intermediate 40.1 (1.00 g, 5.81 mmol) and intermediate 30.2 (0.94 g, 7.64 mmol) in 1,4-dioxane (30 mL), and H2O (12 mL). The resulting mixture was reacted at 110 °C for 16 h. Once cooled to r.t. the reaction was diluted with EtOAc (30 mL) and filtered through a celite pad under vacuum. Collecting the liquor, the two phases were separated and the aqueous phase extracted with EtOAc (2 x 15 mL). The collected organic layers were washed with brine (30 mL), dried over Na2S04, and concentrated under reduced pressure. After chromatographic purification (CH2Cl2/MeOH from 99:1 to 95:5), 0.70 g of the title intermediate 40.2 were obtained. Yield: 71% [00500] MS-ESI(+) m/z: 171.3 (M+H).
40% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 100℃; Inert atmosphere; 1.1 Preparation of 4-pyridin-3-ylaniline (Compound 3)from 3-pyridine boronic acid (Compound 1)And p-bromoaniline (Compound 2) A solution of 4 g (32.5 mmol) of 3-pyridine boronic acid,(29.3 mmo1) p-bromoaniline, 13.5 g (97.5 mmo1)Anhydrous potassium carbonate and 3.8 g (3.25 mmol)The catalyst Pd (PPh3) 4 was dissolved in 90 mL1,4-dioxane and 30 mLWater mixed solvent,Under nitrogen protection at l0 ° C under the reaction overnight,After completion of the reaction, the mixture was cooled to room temperature,The reaction solution was suction filtered, the filter cake was washed with 1,4-dioxane,The filtrate was collected and dried to give a residue,The residue was subjected to column chromatography (elution solvent: petroleum ether: ethyl acetate = 3: 1, volume ratio)To give 2.8 g of 4-pyridin-3-ylaniline in about 40% yield;
35% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 100℃; Inert atmosphere; 4.1.2 4.1.2. 4-Pyridin-3-ylaniline (5) A flask charged with Pd(pddf)Cl2 (0.42 g, 0.58 mmol), KOAc (2.28 g, 23 mmol), and the pinacol ester of diboron (1.62 g, 6.4 mmol) and (1) (1 g, 5.8 mmol) was flushed with nitrogen. 1,4-Dioxane (40 mL) were then added. After being stirred at 100 °C for 5 h under nitrogen atmosphere, the mixture was cooled to room temperature. Compound (3) (0.82 g, 5.2 mmol), H2O (20 mL) and 1,4-dioxane (20 mL) were then added and the mixture was refluxed overnight under nitrogen. In a flask charged with compound (4) (0.8 g, 6.6 mmol), Pd(pddf)Cl2 (0.44 g, 0.6 mmol), compound (1) (1 g, 6 mmol), and K2CO3 (2.5 g, 18 mmol) was flushed with nitrogen. 1,4-Dioxane (60 mL) and water (20 mL) were then added. The mixture was refluxed overnight under nitrogen. The product was extracted with AcOEt (30 mL * 3), washed with water, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 3:1) gave (5) (0.35 g, 35%) as white solid. Mp: 114-116 °C, 1H NMR (400 MHz, CDCl3) δ 8.82 (d, J = 1.6 Hz, 1H), 8.53 (d, J = 4.0 Hz, 1H), 7.83 (d, J = 7.9 Hz, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.33 (m, 1H), 6.81 (d, J = 8.3 Hz, 2H).

  • 39
  • [ 82261-42-5 ]
  • [ 1142945-86-5 ]
  • C29H23N5O2S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tri-tert-butyl phosphine; triethylamine In N,N-dimethyl-formamide; toluene at 180℃; for 0.333333h; Microwave irradiation; 17 In a microwave vial was sequentially added 9 (0.150 g, 0.37 mmol), Pd(OAc)2 (0.008 g, 0.037 mmol), DMF (3 mL), 4-(pyridine-3-yl)aniline (0.076 g, 0.45 mmol), P(J-Bu)3 (1 M in toluene, 0.074 mL, 0.074 mmol), and triethylamine (0.52 mL, 3.71 mmol). The reaction mixture was heated 20 min at 180 0C in a Biotage microwave reactor and then cooled to room temperature. The resulting mixture was added a solution of 1.0 M tetrabutylammonium fluoride in THF (0.5 mL) and stirred 20 min at 110 0C. Upon cooling to room temperature the resulting mixture was separated by preparative HPLC. Fractions that contained the desired product were combined, neutralized with saturated Na2CO3, and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated to afford the title compound as a yellow solid (0.011 g, 8%).[0144] 1H NMR (500 MHz, DMSO-d6): δ 2.28 (s, 3H), 3.35-3.40 (m, IH), 6.91 (dd, J = 3.7, 1.8 Hz, IH), 3.66 (dd, J = 3.5, 2.2 Hz, IH), 7.43 (s, IH), 7.86 (d, J = 8.8 Hz, IH), 7.96 (s, IH), 8.02 (dd, J = 8.1, 5.5 Hz, IH), 8.13 (s, 2H), 8.76 (d, J= 5.5, IH), 8.82 (d, J = 8.2 Hz, IH), 9.22 (d, J = 1.8 Hz, IH), 9.62 (s, IH), 11.80 (s, IH) MS (ES+): m/z 384 (M+H)+
  • 40
  • [ 82261-42-5 ]
  • [ 1147014-58-1 ]
  • C35H29N5O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In N,N-dimethyl-formamide; toluene at 180℃; for 0.333333h; Microwave irradiation; 27 In a microwave vial was sequentially added 9 (0.17 g, 0.37 mmol), Pd(OAc)2 (0.008 g, 0.037 mmol), DMF (3 mL), 4-(pyridine-3-yl)aniline (0.08 g, 0.44 mmol), P(J-Bu)3 (1 M in toluene, 0.073 mL, 0.73 mmol), and TEA (0.52 mL, 3.7 mmol). The reaction mixture was heated for 20 min at 180 0C in a Biotage microwave reactor. The resulting mixture was added I M tetrabutylammonium floride in TηF (1 mL) and stirred for 30 min under reflux. The resulting mixture was separated by preparative ηPLC. Fractions that contained the desired product were combined, neutralized with saturated Na2CO3, and extracted with EtOAc. The organic layer was dried over MgSO4, added 4.0 M HCl in 1,4-dioxane (0.5 mL), and concentrated to afford the title compound as a yellow solid (2.5 mg). [0179] 1H NMR (500 MHz, DMSO-J6): δ 1.34 (d, J = 7.0 Hz, 6H), 3.59 (qn, J = 7.1 Hz, IH), 6.52 (dd, J = 3.5, 1.7 Hz, IH), 7.32 (dd, J= 7.3, 1.8 Hz, IH), 7.38 (dd, J = 3.3, 2.2 Hz, IH), 7.46-7.51 (m, 2H), 7.66 (d, J = 7.3 Hz, IH), 7.85 (d, J = 8.8 Hz, 2H), 8.08 (d, J = 8.8 Hz, 2H), 8.78 (d, J = 5.9 Hz, IH), 8.81 (d, J = 8.4 Hz, IH), 9.22 (s, IH), 9.93 (s, IH), 11.93 (s, IH)[0180] MS (ES+): m/z 430 (M+H)+
  • 41
  • [ 82261-42-5 ]
  • [ 1187890-35-2 ]
  • [ 1187889-95-7 ]
YieldReaction ConditionsOperation in experiment
38.73% Stage #1: 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-propionic acid With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 0.0333333h; Stage #2: 4-pyridin-3-ylaniline In N,N-dimethyl-formamide at 20℃; 44 Synthesis of 3-[4-(2-Bromo-benzoyl)-piperazin-1-yl]-3-oxo-N-(4-pyridin-3-yl-phenyl)-propionamide Example 44 Synthesis of 3-[4-(2-Bromo-benzoyl)-piperazin-1-yl]-3-oxo-N-(4-pyridin-3-yl-phenyl)-propionamide DMAP (68 mg, 0.56 mmol) was added to 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-propionic acid (100 mg, 0.28 mmol) in DMF (2 mL) followed by EDCI (64 mg, 0.33 mmol) and HOBT (45 mg, 0.33 mmol). After 2 minutes, 4-pyridin-3-yl-phenylamine (55 mg, 0.18 mmol) was added and it was stirred at room temperature overnight. Cold water was then added and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure to afford 55 mg (38.73% yield) of 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-N-(4-pyridin-3-yl-phenyl)-propionamide. LC/MS [M+H]+: 507.1, 90.55%. 1H NMR (300 MHz, DMSO-d6): δ 10.25 (d, 1H), 8.9 (bt, 1H), 8.5 (d, 1H), 8.1-8.0 (m, 1H), 7.7 (d, 5H), 7.52-7.3 (m, 4H), 3.8-3.46 (m, 8H), 3.2 (bt, 1H), 3.1 (bt, 1H).
  • 43
  • [ 220565-63-9 ]
  • [ 106-40-1 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
80% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate In tetrahydrofuran at 20℃; for 72h; Inert atmosphere;
  • 44
  • [ 220565-63-9 ]
  • [ 540-37-4 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
86% With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 20℃; for 1h; Inert atmosphere;
  • 45
  • [ 5957-97-1 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
98% With bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; N-[2-(di(1-adamantyl)phosphino)phenyl]morpholine; ammonia; sodium t-butanolate In 1,4-dioxane at 110℃; for 1h; Inert atmosphere; chemoselective reaction;
81% With bis(1,5-cyclooctadiene)nickel (0); (R)-1-[(Sp)-2-(dicyclohexylphosphanyl)ferrocenyl]ethyldicyclohexylphosphane; ammonia; sodium t-butanolate In 1,4-dioxane; toluene at 110℃; for 16h; Sealed tube;
  • 46
  • [ 1692-25-7 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate; bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 2 h / 100 °C 2: hydrogen; palladium 10% on activated carbon / methanol; ethyl acetate / 5 h
Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / 1,4-dioxane; water / 12 h / 100 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen / methanol / 20 °C
Multi-step reaction with 2 steps 1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium acetate / 1,4-dioxane / 3 h / 60 °C / Inert atmosphere 2: iron; hydrogenchloride / 1,4-dioxane; water / 5 h / Reflux
  • 47
  • [ 82261-42-5 ]
  • [ 1438423-93-8 ]
  • [ 1438423-96-1 ]
YieldReaction ConditionsOperation in experiment
90 mg With palladium diacetate; potassium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,4-dioxane at 110℃; for 20h; Inert atmosphere; 29 A mixture of (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)butanamide (100 mg, 0.417 mmol), 4-(pyridin-3-yl)aniline (77 mg, 0.452 mmol), K2CO3 (100 mg, 0.724 mmol), BINAP (30 mg, 0.048 mmol) and Pd(OAc)2 (15 mg, 0.066 mmol) in dioxane (3 mL) was degassed with Ar, then was stirred at 110 C for 20 h. The mixture was concentrated in vacuo. The residue was purified by HPLC to give (R)-2-(5-cyano-6-(4-(pyridin-3-yl)phenylamino)pyrazin-2-ylamino)butanamide (90 mg).
  • 48
  • [ 82261-42-5 ]
  • [ 84-86-6 ]
  • [ 1357165-18-4 ]
YieldReaction ConditionsOperation in experiment
70.4% Stage #1: 4-pyridin-3-ylaniline With hydrogenchloride In water Stage #2: With sodium nitrite In water at 5℃; for 0.0833333h; Stage #3: 4-amino-1-naphthalenesufonic acid In water at 10℃; for 1h; 123.iii (iii) 4-Amino-3-(4-pyridine-3-ylphenylazo)-1-naphthalenesulfonic acid sodium salt 4-(Pyridine-3-yl)aniline (0.75g, 4.4mmol) synthesized in (ii) was suspended in water (7.5ml), and added dropwise with 35% hydrochloric acid (2.29g, 22mmol). The mixture was cooled below 5°C, and added dropwise with an aqueous solution of sodium nitrite (0.32g, 4.6mmol). The reaction was carried out below 5°C for about 5 minutes. After the completion of the reaction, excess sodium nitrite was decomposed with amidosulfuric acid. The mixture was added with 4-amino-1-naphthalenesulfonic acid(0.96g, 4.3mmol) and water (19ml), and neutralized with 10% aqueous sodium hydroxide to pH 7 to 10. The reaction was carried out below 10°C for 1 hour, during which the pH was kept 7 to 10. After the completion of the reaction, the temperature was raised to 40 to 50 °C, and salting-out was performed with addition of sodium chloride. After cooling to the room temperature, the precipitated crystals were filtered with suction. The products were purified by column chromatography followed by recrystallization to give the title compound (1.29g, 70.4%). 1H-NMR (DMSO-d6) δ [ppm] = 8.99 (1H, d, J=1.8), 8.77 (1H, d, J=8.4), 8.59 (1H, dd, J=4.8, 1.2), 8.46 (1H, d, J=8.4), 8.34 (1H, s), 8.17 (1H, d, J=8.1), 8.11(2H, d, J=8.4), 7.90(2H, d, J=8.4), 7.78 (NH2), 7.60(dd, J=7.8, 7.2), 7.52-7.47(2H, m) 13C-NMR(DMSO-d6) δ [ppm] = 152.5, 148.7, 147.7, 146.2, 137.7, 134.9, 134.1, 132.3, 131.8, 128.9, 128.3, 128.2, 127.7, 125.0, 124.2, 124.0, 123.9, 123.0, 117.4
  • 49
  • [ 59020-10-9 ]
  • [ 106-40-1 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
99% With copper(l) iodide; C37H51ClFeNPPd; cesium fluoride; In N,N-dimethyl-formamide; at 80℃; for 12h;Inert atmosphere; General procedure: 4.3.9 3-(4-Aminophenyl)pyridine (3ia) 17 Yellow solid, mp 108-109 C; 1H NMR (400 MHz, CDCl3): delta=8.79 (d, J=1.44 Hz, 1H), 8.50 (d, J=4.04 Hz, 1H), 7.80 (d, J=7.Aryl halide (0.5 mmol), base (1 mmol), CuI (20 mol %), alkylstannylpyridine(0.75 mmol), and catalyst (1 mol %) were dissolvedin DMF (2 mL) in a 10 mL vial and heated at a specific temperatureunder N2 for 12 h. After the reaction was complete, and thenquenched with water. The mixture was diluted with ethyl acetate(10 mL), filtered through a pad of Celite, and followed by extractionwith ethyl acetate for three times. The combined organic layer wasdried over anhydrous Na2SO4, filtered, and evaporated under reducedpressure. The residual was purified by flash chromatographyon silica gel (ethyl acetate/hexane) to give the desired product.88 Hz, 1H), 7.40 (d, J=8.56 Hz, 2H), 7.23-7.32 (m, 1H), 6.78 (d, J=8.36 Hz, 2H), 3.79 (s, 2H); 13C NMR (100 MHz, CDCl3): delta=115.5, 123.4, 127.8, 128.0, 133.4, 136.5, 146.60, 147.4, 147.7; HRMS-ESI (m/z): [M+H]+ calcd for C11H11N2+: 171.0917, found: 171.0919.
  • 50
  • [ 626-55-1 ]
  • [ 214360-73-3 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 100℃; Inert atmosphere; 4.1.2 4.1.2. 4-Pyridin-3-ylaniline (5) A flask charged with Pd(pddf)Cl2 (0.42 g, 0.58 mmol), KOAc (2.28 g, 23 mmol), and the pinacol ester of diboron (1.62 g, 6.4 mmol) and (1) (1 g, 5.8 mmol) was flushed with nitrogen. 1,4-Dioxane (40 mL) were then added. After being stirred at 100 °C for 5 h under nitrogen atmosphere, the mixture was cooled to room temperature. Compound (3) (0.82 g, 5.2 mmol), H2O (20 mL) and 1,4-dioxane (20 mL) were then added and the mixture was refluxed overnight under nitrogen. In a flask charged with compound (4) (0.8 g, 6.6 mmol), Pd(pddf)Cl2 (0.44 g, 0.6 mmol), compound (1) (1 g, 6 mmol), and K2CO3 (2.5 g, 18 mmol) was flushed with nitrogen. 1,4-Dioxane (60 mL) and water (20 mL) were then added. The mixture was refluxed overnight under nitrogen. The product was extracted with AcOEt (30 mL * 3), washed with water, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 3:1) gave (5) (0.35 g, 35%) as white solid. Mp: 114-116 °C, 1H NMR (400 MHz, CDCl3) δ 8.82 (d, J = 1.6 Hz, 1H), 8.53 (d, J = 4.0 Hz, 1H), 7.83 (d, J = 7.9 Hz, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.33 (m, 1H), 6.81 (d, J = 8.3 Hz, 2H).
  • 51
  • [ 175278-09-8 ]
  • [ 82261-42-5 ]
  • [ 32315-10-9 ]
  • N-[4-bromo-2-(trifluoromethoxy)phenyl]-N'-(4-pyridin-3-ylphenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Triphosgene (0.14 g, 0.48 mmol) was dissolved in anhydrous CH2Cl2 (15 mL) and the mixture was stirred on the ice-bath for 15 min. 3-Bromo-5-(trifluoromethyl)aniline (0.3 g, 1.2 mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise to the above mixture and stirring continued for 20 min. Et3N (0.2 mL, 1.44 mmol) diluted with CH2Cl2 (5 mL) was then added into the mixture. Stirring was continued for 20 min and a solution of Et3N (0.2 mL, 1.44 mmol), 4-pyridin-3-ylaniline (5) (0.2 g, 1.2 mmol) in anhydrous CH2Cl2 (20 mL) was added. After completion of the action, the reaction was quenched with dilute Na2CO3. The organic layer was washed with water and brine, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 6:1) yielding (L1). yield 73%
  • 52
  • [ 82261-42-5 ]
  • [ 32315-10-9 ]
  • [ 175278-17-8 ]
  • N-[2-bromo-4-(trifluoromethoxy)phenyl]-N'-(4-pyridin-3-ylphenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Triphosgene (0.14 g, 0.48 mmol) was dissolved in anhydrous CH2Cl2 (15 mL) and the mixture was stirred on the ice-bath for 15 min. 3-Bromo-5-(trifluoromethyl)aniline (0.3 g, 1.2 mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise to the above mixture and stirring continued for 20 min. Et3N (0.2 mL, 1.44 mmol) diluted with CH2Cl2 (5 mL) was then added into the mixture. Stirring was continued for 20 min and a solution of Et3N (0.2 mL, 1.44 mmol), 4-pyridin-3-ylaniline (5) (0.2 g, 1.2 mmol) in anhydrous CH2Cl2 (20 mL) was added. After completion of the action, the reaction was quenched with dilute Na2CO3. The organic layer was washed with water and brine, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 6:1) yielding (L1). yield 73%
  • 53
  • [ 82261-42-5 ]
  • [ 886762-08-9 ]
  • [ 32315-10-9 ]
  • N-[5-bromo-2-(trifluoromethoxy)phenyl]-N'-(4-pyridin-3-ylphenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Triphosgene (0.14 g, 0.48 mmol) was dissolved in anhydrous CH2Cl2 (15 mL) and the mixture was stirred on the ice-bath for 15 min. 3-Bromo-5-(trifluoromethyl)aniline (0.3 g, 1.2 mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise to the above mixture and stirring continued for 20 min. Et3N (0.2 mL, 1.44 mmol) diluted with CH2Cl2 (5 mL) was then added into the mixture. Stirring was continued for 20 min and a solution of Et3N (0.2 mL, 1.44 mmol), 4-pyridin-3-ylaniline (5) (0.2 g, 1.2 mmol) in anhydrous CH2Cl2 (20 mL) was added. After completion of the action, the reaction was quenched with dilute Na2CO3. The organic layer was washed with water and brine, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 6:1) yielding (L1). yield 73%
  • 54
  • [ 82261-42-5 ]
  • [ 32315-10-9 ]
  • [ 887267-47-2 ]
  • N-[2-bromo-5-(trifluoromethoxy)phenyl]-N'-(4-pyridin-3-ylphenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Triphosgene (0.14 g, 0.48 mmol) was dissolved in anhydrous CH2Cl2 (15 mL) and the mixture was stirred on the ice-bath for 15 min. 3-Bromo-5-(trifluoromethyl)aniline (0.3 g, 1.2 mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise to the above mixture and stirring continued for 20 min. Et3N (0.2 mL, 1.44 mmol) diluted with CH2Cl2 (5 mL) was then added into the mixture. Stirring was continued for 20 min and a solution of Et3N (0.2 mL, 1.44 mmol), 4-pyridin-3-ylaniline (5) (0.2 g, 1.2 mmol) in anhydrous CH2Cl2 (20 mL) was added. After completion of the action, the reaction was quenched with dilute Na2CO3. The organic layer was washed with water and brine, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 6:1) yielding (L1). yield 73%
  • 55
  • [ 82261-42-5 ]
  • [ 32315-10-9 ]
  • [ 554-00-7 ]
  • N-(2,4-dichlorophenyl)-N'-(4-pyridin-3-ylphenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: bis(trichloromethyl) carbonate; 2,4-Dichloroaniline In dichloromethane at 20℃; for 0.333333h; Cooling with ice; Stage #2: With triethylamine In dichloromethane at 20℃; for 0.333333h; Stage #3: 4-pyridin-3-ylaniline With triethylamine In dichloromethane at 20℃; 4.1.3 4.1.3. N-[3-Bromo-5-(trifluoromethyl)phenyl]-N'-(4-pyridin-3-ylphenyl)urea (L1) General procedure: Triphosgene (0.14 g, 0.48 mmol) was dissolved in anhydrous CH2Cl2 (15 mL) and the mixture was stirred on the ice-bath for 15 min. 3-Bromo-5-(trifluoromethyl)aniline (0.3 g, 1.2 mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise to the above mixture and stirring continued for 20 min. Et3N (0.2 mL, 1.44 mmol) diluted with CH2Cl2 (5 mL) was then added into the mixture. Stirring was continued for 20 min and a solution of Et3N (0.2 mL, 1.44 mmol), 4-pyridin-3-ylaniline (5) (0.2 g, 1.2 mmol) in anhydrous CH2Cl2 (20 mL) was added. After completion of the action, the reaction was quenched with dilute Na2CO3. The organic layer was washed with water and brine, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 6:1) yielding (L1). yield 73%
  • 56
  • [ 82261-42-5 ]
  • [ 32315-10-9 ]
  • [ 3863-11-4 ]
  • N-(3,4-difluorophenyl)-N'-(4-pyridin-3-ylphenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: bis(trichloromethyl) carbonate; 3,4-difluoroaniline In dichloromethane at 20℃; for 0.333333h; Cooling with ice; Stage #2: With triethylamine In dichloromethane at 20℃; for 0.333333h; Stage #3: 4-pyridin-3-ylaniline With triethylamine In dichloromethane at 20℃; 4.1.3 4.1.3. N-[3-Bromo-5-(trifluoromethyl)phenyl]-N'-(4-pyridin-3-ylphenyl)urea (L1) General procedure: Triphosgene (0.14 g, 0.48 mmol) was dissolved in anhydrous CH2Cl2 (15 mL) and the mixture was stirred on the ice-bath for 15 min. 3-Bromo-5-(trifluoromethyl)aniline (0.3 g, 1.2 mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise to the above mixture and stirring continued for 20 min. Et3N (0.2 mL, 1.44 mmol) diluted with CH2Cl2 (5 mL) was then added into the mixture. Stirring was continued for 20 min and a solution of Et3N (0.2 mL, 1.44 mmol), 4-pyridin-3-ylaniline (5) (0.2 g, 1.2 mmol) in anhydrous CH2Cl2 (20 mL) was added. After completion of the action, the reaction was quenched with dilute Na2CO3. The organic layer was washed with water and brine, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 6:1) yielding (L1). yield 73%
  • 57
  • [ 82261-42-5 ]
  • [ 32315-10-9 ]
  • [ 95-76-1 ]
  • N-(3,4-dichlorophenyl)-N'-(4-pyridin-3-ylphenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: bis(trichloromethyl) carbonate; m,p-dichloroaniline In dichloromethane at 20℃; for 0.333333h; Cooling with ice; Stage #2: With triethylamine In dichloromethane at 20℃; for 0.333333h; Stage #3: 4-pyridin-3-ylaniline With triethylamine In dichloromethane at 20℃; 4.1.3 4.1.3. N-[3-Bromo-5-(trifluoromethyl)phenyl]-N'-(4-pyridin-3-ylphenyl)urea (L1) General procedure: Triphosgene (0.14 g, 0.48 mmol) was dissolved in anhydrous CH2Cl2 (15 mL) and the mixture was stirred on the ice-bath for 15 min. 3-Bromo-5-(trifluoromethyl)aniline (0.3 g, 1.2 mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise to the above mixture and stirring continued for 20 min. Et3N (0.2 mL, 1.44 mmol) diluted with CH2Cl2 (5 mL) was then added into the mixture. Stirring was continued for 20 min and a solution of Et3N (0.2 mL, 1.44 mmol), 4-pyridin-3-ylaniline (5) (0.2 g, 1.2 mmol) in anhydrous CH2Cl2 (20 mL) was added. After completion of the action, the reaction was quenched with dilute Na2CO3. The organic layer was washed with water and brine, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 6:1) yielding (L1). yield 73%
  • 58
  • [ 82261-42-5 ]
  • [ 32315-10-9 ]
  • [ 328-74-5 ]
  • N-[3,5-bis(trifluoromethyl)phenyl]-N'-(4-pyridin-3-ylphenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: bis(trichloromethyl) carbonate; 3,5-Bis-(trifluoromethyl)aniline In dichloromethane at 20℃; for 0.333333h; Cooling with ice; Stage #2: With triethylamine In dichloromethane at 20℃; for 0.333333h; Stage #3: 4-pyridin-3-ylaniline With triethylamine In dichloromethane at 20℃; 4.1.3 4.1.3. N-[3-Bromo-5-(trifluoromethyl)phenyl]-N'-(4-pyridin-3-ylphenyl)urea (L1) General procedure: Triphosgene (0.14 g, 0.48 mmol) was dissolved in anhydrous CH2Cl2 (15 mL) and the mixture was stirred on the ice-bath for 15 min. 3-Bromo-5-(trifluoromethyl)aniline (0.3 g, 1.2 mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise to the above mixture and stirring continued for 20 min. Et3N (0.2 mL, 1.44 mmol) diluted with CH2Cl2 (5 mL) was then added into the mixture. Stirring was continued for 20 min and a solution of Et3N (0.2 mL, 1.44 mmol), 4-pyridin-3-ylaniline (5) (0.2 g, 1.2 mmol) in anhydrous CH2Cl2 (20 mL) was added. After completion of the action, the reaction was quenched with dilute Na2CO3. The organic layer was washed with water and brine, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 6:1) yielding (L1). yield 73%
  • 59
  • [ 82261-42-5 ]
  • [ 32315-10-9 ]
  • [ 54962-75-3 ]
  • N-[3-bromo-5-(trifluoromethyl)phenyl]-N'-(4-pyridin-3-ylphenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% 4.1.3 N-[3-Bromo-5-(trifluoromethyl)phenyl]-N'-(4-pyridin-3-ylphenyl)urea (L1) Triphosgene (0.14 g, 0.48 mmol) was dissolved in anhydrous CH2Cl2 (15 mL) and the mixture was stirred on the ice-bath for 15 min. 3-Bromo-5-(trifluoromethyl)aniline (0.3 g, 1.2 mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise to the above mixture and stirring continued for 20 min. Et3N (0.2 mL, 1.44 mmol) diluted with CH2Cl2 (5 mL) was then added into the mixture. Stirring was continued for 20 min and a solution of Et3N (0.2 mL, 1.44 mmol), 4-pyridin-3-ylaniline (5) (0.2 g, 1.2 mmol) in anhydrous CH2Cl2 (20 mL) was added. After completion of the action, the reaction was quenched with dilute Na2CO3. The organic layer was washed with water and brine, and dried over Na2SO4. After filtration and concentration in vacuo, the residues was purified by silica gel flash chromatography (PE/AcOEt = 6:1) yielding (L1). yield 73percent, mp: 200-202 °C, 1H NMR (400 MHz, DMSO) delta 9.28 (s, 1H), 9.12 (s, 1H), 8.89 (d, J = 2.0 Hz, 1H), 8.53 (m, 1H), 8.08-8.03 (m, 1H), 7.98 (s, 1H), 7.89 (s, 1H), 7.70 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.6 Hz, 2H), 7.53 (s, 1H), 7.46 (m, 1H). 13C NMR (101 MHz, DMSO) delta 152.71, 148.39, 147.71, 142.59, 139.77, 135.60, 133.93, 131.84, 131.52, 131.35, 127.72, 124.54, 124.26, 122.81, 121.02, 119.60, 113.97, 113.93.
  • 60
  • [ 82261-42-5 ]
  • [ 79-04-9 ]
  • 2-chloro-N-(4-(pyridin-3-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; 2 6.1.5. General procedure for the synthesis of 10-12 General procedure: To a solution of corresponding amine (1 equiv) and Et3N (1.2 equiv) in dry dichloromethane (5 mL) was added chloroacetyl chloride (1.1 equiv) slowly at 0 °C under N2. After stirred at room temperature overnight, the mixture was diluted with water (30 mL) and extracted with dichloromethane (30 mL x 3). The combined organic layer was dried over Na2SO4 and concentrated.The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to afford the desired products 10-12. 6.1.5.2 2-Chloro-N-(4-(pyridin-3-yl)phenyl)acetamide (11) Yellow solid (yield: 67%). 1H NMR (400 MHz, DMSO-d6): δ 10.46 (s, 1H), 8.88 (s, 1H), 8.54 (d, J = 4.4 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.73 (s, 4H), 7.47 (dd, J = 8.0, 5.2 Hz, 1H), 4.29 (s, 2H).
67% With triethylamine In dichloromethane at 20℃; for 12h; Cooling with ice; 1.31.1 Synthesis of B31-2 The B31 - 1 (120 mg, 0 . 71 mmol) and triethylamine (86 mg, 0 . 85 mmol) dissolved in dichloromethane (5 ml) in, under ice bath slowly adding 2 - chloropropionyl (88 mg, 0 . 78 mmol), stirring at room temperature 12 hours, the addition of water (50 ml), ethyl acetate (50 ml * 3) extraction, the combined organic phase, saturated salt water (30 ml * 2) washing, dried with anhydrous sodium sulfate, concentrated under reduced pressure by column chromatography (dichloromethane: methanol=60:1) to get the yellow solid (116 mg, 67%).
  • 61
  • [ 82261-42-5 ]
  • [ 36950-95-5 ]
  • 2-(9H-fluoren-2-yl)-N-(4-(pyridin-3-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 12h; 1 General procedure for the synthesis of compounds 16-19 and 21 General procedure: To a solution of 3 or 6 (1 eq), corresponding acid (1 eq) and N,Ndiisopropylethylamine(5 eq) in DMF (1.5 mL) was added HATU (1eq). After stirring at room temperature for 12 h, the mixture wasdiluted with water (50 mL) and extracted with ethyl acetate (50 mLx 3). The combined organic layers werewashed with brine (50 mL x3), dried over Na2SO4 and concentrated. The residue was purifiedby silica gel column chromatography (dichloromethane/methanol)to give the desired products 16-19 and 21. 6.1.6.1 2-(9H-Fluoren-2-yl)-N-(4-(pyridin-3-yl)phenyl)acetamide (16) White solid (60%); 1H NMR (400 MHz, DMSO-d6) δ 10.37 (s, 1H), 8.87 (d, J = 2.4 Hz, 1H), 8.52 (dd, J = 4.4, 0.8 Hz, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.89-7.84 (m, 2H), 7.76 (d, J = 8.8 Hz, 2H), 7.70 (d, J = 8.8 Hz, 2H), 7.60-7.56 (m, 2H), 7.45 (dd, J = 8.0, 4.8 Hz, 1H), 7.39-7.35 (m, 2H), 7.32-7.28 (m, 1H), 3.92 (s, 2H), 3.75 (s, 2H). ESI-MS (m/z): 377.2 [M+H]+.
  • 62
  • [ 82261-42-5 ]
  • [ 53076-71-4 ]
  • 2-(9-oxo-9H-fluoren-2-yl)-N-(4-(pyridin-3-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 12h; 2 General procedure for the synthesis of compounds 16-19 and 21 General procedure: To a solution of 3 or 6 (1 eq), corresponding acid (1 eq) and N,Ndiisopropylethylamine(5 eq) in DMF (1.5 mL) was added HATU (1eq). After stirring at room temperature for 12 h, the mixture wasdiluted with water (50 mL) and extracted with ethyl acetate (50 mLx 3). The combined organic layers werewashed with brine (50 mL x3), dried over Na2SO4 and concentrated. The residue was purifiedby silica gel column chromatography (dichloromethane/methanol)to give the desired products 16-19 and 21.
  • 63
  • [ 82261-42-5 ]
  • [ 92151-86-5 ]
  • 2-(dibenzo[b,d]furan-3-yl)-N-(4-(pyridin-3-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 12h; 3 General procedure for the synthesis of compounds 16-19 and 21 General procedure: To a solution of 3 or 6 (1 eq), corresponding acid (1 eq) and N,Ndiisopropylethylamine(5 eq) in DMF (1.5 mL) was added HATU (1eq). After stirring at room temperature for 12 h, the mixture wasdiluted with water (50 mL) and extracted with ethyl acetate (50 mLx 3). The combined organic layers werewashed with brine (50 mL x3), dried over Na2SO4 and concentrated. The residue was purifiedby silica gel column chromatography (dichloromethane/methanol)to give the desired products 16-19 and 21.
  • 64
  • [ 82261-42-5 ]
  • 4-(cyclopropyloxy)-3-[(morpholin-4-ylacetyl)amino]benzoyl chloride [ No CAS ]
  • 4-(cyclopropyloxy)-3-[(morpholin-4-ylacetyl)amino]-N-[4-(pyridin-3-yl)phenyl]benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85 mg With pyridine In toluene at 100℃; for 5h; 35 4-(cyclopropyloxy)-3-[(morpholin-4-ylacetyl)amino]-N-[4-(pyridin-3-yl)phenyl]ben Step 1: 900 mg (2.81 mmol) of 4-(cyclopropyloxy)-3-[(morpholin-4-ylacetyl)amino]benzoic acid (intermediate 29) were suspended in 9 mL of anh toluene. 5.3 mL (118.4 mmol) of thionyl dichloride were added and it was stirred for 2 h at 70 °C. The reaction mixture was concentrated and the residue was used without further purification in the next step. Step 2: 140 mg (0.41 mmol) of 4-(cyclopropyloxy)-3-[(morpholin-4-ylacetyl)amino]benzoyl chloride (the material from step 1) were suspended in 4 mL of anh toluene. 1 mL of anh pyridine and 84 mg (0.50 mmol) of 4-(pyridin-3-yl)aniline were added and it was stirred for 5 h at 100 °C. The reaction mixture was allowed to reach rt, stirred over night and concentrated. The residue was purified by HPLC (Waters XBrigde C18 5μ 100x30mm; water + 0.2% vol. ammonia (32%) / methanol gradient; temperature: rt; injection: 4000 μ; DAD scan: 210-400 nm) to afford 85 mg (43% of theory) of the title compound. 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.754 (0.69), 0.761 (0.87), 0.768 (2.13), 0.774 (3.48), 0.780 (2.43), 0.785 (1.70), 0.792 (1.01), 0.906 (0.81), 0.921 (2.83), 0.927 (2.08), 0.935 (2.30), 0.939 (2.44), 0.941 (2.36), 0.956 (0.62), 0.968 (0.87), 1.109 (16.00), 1.146 (0.62), 2.327 (0.58), 2.331 (0.42), 2.523 (1.58), 2.546 (3.55), 2.558 (5.16), 2.569 (3.86), 2.665 (0.43), 2.669 (0.60), 2.673 (0.44), 3.164 (11.16), 3.659 (3.85), 3.671 (5.50), 3.682 (3.94), 4.096 (0.45), 4.103 (0.87), 4.111 (1.27), 4.118 (1.73), 4.125 (1.26), 4.133 (0.89), 4.140 (0.44), 4.177 (1.47), 7.447 (3.56), 7.455 (1.69), 7.457 (1.74), 7.469 (5.50), 7.474 (1.65), 7.477 (1.79), 7.489 (1.67), 7.725 (0.63), 7.732 (5.00), 7.737 (1.80), 7.749 (2.10), 7.754 (6.61), 7.758 (3.11), 7.763 (2.49), 7.779 (1.87), 7.785 (1.91), 7.893 (0.89), 7.899 (6.42), 7.905 (1.94), 7.916 (1.76), 7.922 (4.91), 7.928 (0.61), 8.065 (1.31), 8.070 (1.65), 8.076 (1.37), 8.085 (1.32), 8.091 (1.66), 8.096 (1.32), 8.532 (2.58), 8.536 (2.53), 8.545 (2.48), 8.548 (2.43), 8.780 (3.80), 8.786 (3.76), 8.907 (2.96), 8.909 (3.18), 8.914 (3.04), 9.701 (3.33), 10.300 (4.12). LC-MS (Method 4): Rt = 1.18 min; MS (ESIpos): m/z = 473 [M+H]+.
  • 65
  • [ 82261-42-5 ]
  • C16H14N4O4S [ No CAS ]
  • 2-(5-phenyl-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)-N-(4-(pyridin-3-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran; benzene at 50℃; for 6h; General precedure for amidation. General procedure: The solution of triazole 13 (1.0 equiv) in a mixture of trifluoroacetic acid and methylene chloride (1:2) was stirred at 35 °C for 3 h. The solvent was then removed by vacuum and the residue was dissolved in tetrahydrofuran. Triethylamine (1.1 equiv) and methanesulfonyl chloride (1.1 equiv) were subsequently added. After stirring at 23 °C for 3 h, a solution of arylamine (1.2 equiv) and Hünig’s base (5.0 equiv) in a mixture of tetrahydrofuran and benzene (1:4) was added. After stirring at 50 °C for 16 h, the mixture was quenched with saturated ammonium chloride and extracted with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. The solvent was then removed under vacuum and the residue was purified by a flash column chromatography on silica gel to give 14.
  • 66
  • [ 955947-86-1 ]
  • [ 82261-42-5 ]
  • C19H13BrF3N3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% In dichloromethane at 20℃; for 20h; Cooling with ice; 1.4 0.48 g (2.84 mmol) of 1-hydroxy-2- 4-pyridin-3-ylaniline was dissolved in an ice bath,A solution of 0.8 g (2.84 mmol) of 1-bromo-3-isothiocyanato-5- (trifluoromethyl) benzene in methylene chloride was added dropwise to the above solution,Ice bath for 2 h, then reacted at room temperature for 18 h,After the completion of the reaction, two-thirds of the reaction solution was vacuum-That is a white solid precipitation,I.e., a diarylthiourea compound having an antitumor activity of 0.4 g,The yield was about 50%
  • 67
  • [ 82261-42-5 ]
  • [ 6590-94-9 ]
  • C18H13Cl2N3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% In dichloromethane at 20℃; for 20h; Cooling with ice; 2.4 Reaction of 4-pyridin-3-ylaniline (compound 3) and 1,2-dichloro-4-isothiocyanic acid (compound 13) to obtain a diarylthiourea compound having antitumor activity 1.76 mmol) of 4-pyridin-3-ylaniline was dissolved in anhydrous methylene chloride,Under ice-cooling, 0.33 g (1.6 mmol) of 1,Dichloro-4-isothiocyanic acid in methylene chloride is added dropwise to the above solution,Ice bath for 2 h, then reacted at room temperature for 18 h,After the completion of the reaction, two-thirds of the reaction solution was vacuum-That is a white solid precipitation,That is, with the antitumor activity of diaryl thiourea compounds ○. 2g,The yield was about 40%.
  • 68
  • [ 82261-42-5 ]
  • 3-(4-(((2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl) propanoyl)oxy)methyl)-1H-1,2,3-triazol-1-yl)propanoic acid [ No CAS ]
  • (1-(3-oxo-3-((4-(pyridin-3-yl)phenyl)amino)propyl)-1H-1,2,3-triazol-4-yl)methyl-2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 16h;
  • 69
  • [ 82261-42-5 ]
  • 2-(4-((2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)acetoxy)methyl)-1H-1,2,3-triazol-1-yl)acetic acid [ No CAS ]
  • (1-(2-oxo-2-((4-(pyridin-3-yl)phenyl)amino)ethyl)-1H-1,2,3-triazol-4-yl)methyl-2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 16h;
  • 70
  • [ 82261-42-5 ]
  • 2-(4-(((2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)propanoyl)oxy)methyl)-1H-1,2,3-triazol-1-yl)acetic acid [ No CAS ]
  • (1-(2-oxo-2-((4-(pyridin-3-yl)phenyl)amino)ethyl)-1H-1,2,3-triazol-4-yl)methyl-2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 16h;
  • 71
  • [ 106-47-8 ]
  • [ 1692-25-7 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
89% With Pd(Cy*Phine)2Cl2 ; potassium hydroxide In butan-1-ol at 100℃; for 3h; Glovebox; Inert atmosphere; Schlenk technique;
25% With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 100℃; Inert atmosphere;
  • 72
  • [ 626-60-8 ]
  • [ 106-47-8 ]
  • [ 82261-42-5 ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: 4-chloro-aniline With tetrahydroxydiboron; dicyclohexyl(2',4',6'-triisopropyl-[1,1':3',1''-terphenyl]-2-yl)phosphane; Pd(Cy*Phine)2Cl2 ; potassium acetate In butan-1-ol at 80℃; for 0.5h; Glovebox; Inert atmosphere; Schlenk technique; Sealed tube; Stage #2: 3-Chloropyridine With potassium carbonate In water; butan-1-ol at 80℃; for 1.5h; Inert atmosphere; Glovebox; Schlenk technique; Sealed tube;
  • 73
  • [ 82261-42-5 ]
  • [ 108-41-8 ]
  • 3-methyl-N-(4-(pyridin-3-yl)phenyl)aniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
91 mg With t-BuBrettPhos; palladium diacetate; sodium hydroxide In ethanol; water; toluene; <i>tert</i>-butyl alcohol at 100℃; for 2h; Glovebox; Inert atmosphere; Schlenk technique;
  • 74
  • [ 14508-49-7 ]
  • [ 82261-42-5 ]
  • N-(4-(pyridin-3-yl)phenyl)pyrazin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
69.9 mg With t-BuBrettPhos; palladium diacetate; sodium hydroxide In ethanol; water; toluene; <i>tert</i>-butyl alcohol at 100℃; for 16h; Glovebox; Inert atmosphere; Schlenk technique;
  • 75
  • [ 82261-42-5 ]
  • [ 90-11-9 ]
  • N-(4-(pyridin-3-yl)phenyl)naphthalen-1-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
95.4 mg With t-BuBrettPhos; palladium diacetate; sodium hydroxide In ethanol; water; toluene; <i>tert</i>-butyl alcohol at 100℃; for 16h; Glovebox; Inert atmosphere; Schlenk technique;
  • 76
  • [ 82261-42-5 ]
  • 2-(6-methyl-5,7-dioxo-2,3,4,5,6,7-hexahydro-1H-pyrrolo[3,4-b]pyridin-1-yl)acetic acid [ No CAS ]
  • 2-(6-methyl-5,7-dioxo-2,3,4,5,6,7-hexahydro-1H-pyrrolo[3,4-b]pyridin-1-yl)-N-(4-(pyridin-3-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 16h;
  • 77
  • [ 82261-42-5 ]
  • [ 56044-12-3 ]
  • 2,4-dioxo-N-[4-(3-pyridyl)phenyl]-1H-quinazoline-6-sulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With N-ethyl-N,N-diisopropylamine In tetrahydrofuran
  • 78
  • [ 82261-42-5 ]
  • 3-(4-azidophenyl )pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% Stage #1: 4-pyridin-3-ylaniline With boron trifluoride diethyl etherate In tetrahydrofuran for 0.0833333h; Stage #2: With tert-butyl 2-methylpropanoate In tetrahydrofuran; pentane at -5 - 25℃; for 2h; Stage #3: With sodium azide In water; acetonitrile at 80℃; for 1h; 38 Example 38 Preparation of 4-(3-pyridyl))-phenylazide (Intermediate 2l) The product of the previous step of 300m 4-(3-pyridyl))-phenylamine (Intermediate 1l) was dissolved in analytically pure tetrahydrofuran.(10 ml), slowly dropped into a reaction flask containing (1.5 ml) of boron trifluoride diethyl ether solution at minus 15 times. After reacting for 5 minutes, 0.9 ml of isobutyl tert-butoxide was added dropwise, and the reaction was carried out for 2 hours. Observe the precipitation, the reaction was warmed to minus 5 temperature and 10 ml of n-pentane was added. Then, the temperature was raised to 25 ° C, 10 ml of n-pentane was added, and the filter cake was added to the filter to be placed in a new reaction flask, followed by 294 mg of sodium azide. 30ml (acetonitrile: water = 3:1), reacted at 80 ° C for 1 h. After TLC monitoring reaction was completed, the post-treatment was distilled under reduced pressure to about 10 ml, and the solution was poured into a separating funnel and extracted with dichloromethane for 2-3 times. The water was dried over Na 2 SO 4 , filtered, and evaporated to dryness to give a white oily oily residue, which was purified by petroleum ether: ethyl acetate = 15:1 silica gel column chromatography to give a pale yellow oily liquid about 210 mg, yield 61%.
  • 79
  • [ 82261-42-5 ]
  • 2-(2-(cyclopropanesulfonamido)thiazol-4-yl)butanoic acid [ No CAS ]
  • 2-(2-(cyclopropanesulfonamido)thiazol-4-yl)-N-(4-(pyridin-3-yl)phenyl)butanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
66.5% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 2h; 2-(2-(cyclopropanesulfonamido)thiazol-4-yl)-N-(4-(pyridin-3-yl)phenyl)butanamide T5 HATU (314 mg, 0.83 mmol) was added to a solution of 2-(2-(cyclopropanesulfonamido)thiazol-4- yl)butanoic acid INTB38 (200 mg, 0.69 mmol), 4-(pyridin-3-yl)aniline (Xing-Li et al., 2009) (1 17 mg, 0.69 mmol) and DIPEA (3.6 ml_, 2.07 mmol) in DCM (2 ml.) at RT. The reaction was stirred at RT for 2 hrs. Water (10 ml.) was added and the phases were separated. The solvent was removed to give a brown oil. The crude product was purified by chromatography on silica gel (24 g column, 0-10% MeOH/DCM) to afford 2-(2-(cyclopropanesulfonamido)thiazol-4-yl)-N-(4- (pyridin-3-yl)phenyl)butanamide (207 mg, 0.458 mmol, 66.5 % yield) as a pale orange solid; Rt 1 .29 min (HPLC acidic); m/z 443 (M+H)+ (ES+); 1H NMR (400 MHz, DMSO-d6) d 12.59 (s, 1 H), 10.29 (s, 1 H), 8.89 (dd, J = 2.4, 0.9 Hz, 1 H), 8.54 (dd, J = 4.7, 1 .6 Hz, 1 H), 8.06 (ddd, J = 8.0, 2.5, 1 .6 Hz, 1 H), 7.78 - 7.65 (m, 4H), 7.47 (ddd, J = 7.9, 4.7, 0.8 Hz, 1 H), 6.59 - 6.52 (m, 1 H), 3.60 (t, J = 7.4 Hz, 1 H), 2.65 - 2.55 (m, 1 H), 2.03 - 1 .83 (m, 2H), 0.97 - 0.83 (m, 7H)
Same Skeleton Products
Historical Records

Similar Product of
[ 82261-42-5 ]

Chemical Structure| N/A

A747111[ N/A ]

Bis(4-(pyridin-3-yl)aniline) tetrahydrochloride hydrate

Reason: Free-Salt

Related Functional Groups of
[ 82261-42-5 ]

Aryls

Chemical Structure| 181633-34-1

[ 181633-34-1 ]

5-(Pyridin-3-yl)-[1,1'-biphenyl]-3-amine

Similarity: 0.97

Chemical Structure| 57976-57-5

[ 57976-57-5 ]

3-(Pyridin-3-yl)benzenamine

Similarity: 0.97

Chemical Structure| 1049789-92-5

[ 1049789-92-5 ]

3-(Pyridin-3-yl)aniline hydrochloride

Similarity: 0.94

Chemical Structure| 1235380-44-5

[ 1235380-44-5 ]

3-(Pyridin-3-yl)aniline dihydrochloride

Similarity: 0.94

Chemical Structure| 177202-83-4

[ 177202-83-4 ]

2-(Pyridin-3-yl)aniline

Similarity: 0.92

Amines

Chemical Structure| 181633-34-1

[ 181633-34-1 ]

5-(Pyridin-3-yl)-[1,1'-biphenyl]-3-amine

Similarity: 0.97

Chemical Structure| 57976-57-5

[ 57976-57-5 ]

3-(Pyridin-3-yl)benzenamine

Similarity: 0.97

Chemical Structure| 1049789-92-5

[ 1049789-92-5 ]

3-(Pyridin-3-yl)aniline hydrochloride

Similarity: 0.94

Chemical Structure| 1235380-44-5

[ 1235380-44-5 ]

3-(Pyridin-3-yl)aniline dihydrochloride

Similarity: 0.94

Chemical Structure| 177202-83-4

[ 177202-83-4 ]

2-(Pyridin-3-yl)aniline

Similarity: 0.92

Related Parent Nucleus of
[ 82261-42-5 ]

Pyridines

Chemical Structure| 181633-34-1

[ 181633-34-1 ]

5-(Pyridin-3-yl)-[1,1'-biphenyl]-3-amine

Similarity: 0.97

Chemical Structure| 57976-57-5

[ 57976-57-5 ]

3-(Pyridin-3-yl)benzenamine

Similarity: 0.97

Chemical Structure| 1049789-92-5

[ 1049789-92-5 ]

3-(Pyridin-3-yl)aniline hydrochloride

Similarity: 0.94

Chemical Structure| 1235380-44-5

[ 1235380-44-5 ]

3-(Pyridin-3-yl)aniline dihydrochloride

Similarity: 0.94

Chemical Structure| 177202-83-4

[ 177202-83-4 ]

2-(Pyridin-3-yl)aniline

Similarity: 0.92