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[ CAS No. 1018505-59-3 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 1018505-59-3
Chemical Structure| 1018505-59-3
Chemical Structure| 1018505-59-3
Structure of 1018505-59-3 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1018505-59-3 ]

CAS No. :1018505-59-3 MDL No. :MFCD10009575
Formula : C11H18N4 Boiling Point : -
Linear Structure Formula :- InChI Key :QKUYGFBCRZYCEB-UHFFFAOYSA-N
M.W : 206.29 Pubchem ID :28411599
Synonyms :

Calculated chemistry of [ 1018505-59-3 ]

Physicochemical Properties

Num. heavy atoms : 15
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.55
Num. rotatable bonds : 2
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 69.71
TPSA : 45.39 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.98 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.06
Log Po/w (XLOGP3) : 0.81
Log Po/w (WLOGP) : 0.05
Log Po/w (MLOGP) : 0.67
Log Po/w (SILICOS-IT) : 0.59
Consensus Log Po/w : 0.84

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.79
Solubility : 3.32 mg/ml ; 0.0161 mol/l
Class : Very soluble
Log S (Ali) : -1.34
Solubility : 9.32 mg/ml ; 0.0452 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.25
Solubility : 1.17 mg/ml ; 0.00568 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.2

Safety of [ 1018505-59-3 ]

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

Application In Synthesis of [ 1018505-59-3 ]

* 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 [ 1018505-59-3 ]

[ 1018505-59-3 ] Synthesis Path-Downstream   1~29

  • 3
  • [ 1333509-28-6 ]
  • [ 1018505-59-3 ]
  • [ 1333509-29-7 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate;palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In 1,4-dioxane; for 18.0h;Inert atmosphere; Reflux; A mixture of 5-(4-ethylpiperazin-l -yl)pyridin-2-amine (3.30 g, 16.0 mmol), 6,8- dibromo-5-ethylimidazo[l ,2-a]pyridine (5.00 g, 16.4 mmol), 2,2'-bis(diphenylphosphino)- Iota , Gamma-binaphthalene (2.14 g, 3.44 mmol) and cesium carbonate (16.4 g, 50.5 mmol) in 1 ,4- dioxane (200 mL) was sparged with nitrogen while stirring for 10 min. Palladium(II) acetate (368 mg, 1.51 mmol) was then added and the reaction stirred at reflux for 18 h. After this time, the reaction was cooled to room temperature, diluted with a mixture of 1 : 1methanol/methylene chloride (200 mL) and filtered through a pad of diatomaceous earth. The filtrate was concentrated under reduced pressure and the resulting residue purified by chromatography (silica, gradient, 1 :24 methanol/methylene chloride to 2:23methanol/methylene chloride) to afford 6-bromo-5-ethyl-N-(5-(4-ethylpiperazin-l-yl)pyridin- 2-yl)imidazo| 1 ,2-i/jpyridin-8-amine as a brown solid: NMR (400 MHz, CDC13) d 8.40 (s, 1 H), 8.03 (d, J= 2.8 Hz, 1H), 7.76 (s, 1H), 7.54 (s, 2H), 7.28-7.25 (m, 1H), 6.84 (d, J= 9.2 Hz, 1 H), 3.18-3.13 (m, 4H), 3.10 (q, J = 7.6 Hz, 2H), 2.64 2.60 (m, 4H), 2.49 (q, J= 7.2 Hz, 2H), 1.28 (t, J = 7.6 Hz, 3H), 1.13 (t, J= 7.2 Hz, 3H).
With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In 1,4-dioxane; for 18.0h;Inert atmosphere; Reflux; Preparation of 6-bromo-5-ethyl-N-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)imidazo[1,2-a]pyridin-8-amine A mixture of <strong>[1018505-59-3]5-(4-ethylpiperazin-1-yl)pyridin-2-amine</strong> (3.30 g, 16.0 mmol), 6,8-dibromo-5-ethylimidazo[1,2-a]pyridine (5.00 g, 16.4 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (2.14 g, 3.44 mmol) and cesium carbonate (16.4 g, 50.5 mmol) in 1,4-dioxane (200 mL) was sparged with nitrogen while stirring for 10 min. Palladium(II) acetate (368 mg, 1.51 mmol) was then added and the reaction stirred at reflux for 18 h. After this time, the reaction was cooled to room temperature, diluted with a mixture of 1:1 methanol/methylene chloride (200 mL) and filtered through a pad of diatomaceous earth. The filtrate was concentrated under reduced pressure and the resulting residue purified by chromatography (silica, gradient, 1:24 methanol/methylene chloride to 2:23 methanol/methylene chloride) to afford 6-bromo-5-ethyl-N-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)imidazo[1,2-a]pyridin-8-amine as a brown solid: 1H NMR (400 MHz, CDCl3) d 8.40 (s, 1H), 8.03 (d, J=2.8 Hz, 1H), 7.76 (s, 1H), 7.54 (s, 2H), 7.28-7.25 (m, 1H), 6.84 (d, J=9.2 Hz, 1H), 3.18-3.13 (m, 4H), 3.10 (q, J=7.6 Hz, 2H), 2.64-2.60 (m, 4H), 2.49 (q, J=7.2 Hz, 2H), 1.28 (t, J=7.6 Hz, 3H), 1.13 (t, J=7.2 Hz, 3H).
  • 4
  • [ 1333509-28-6 ]
  • [ 1018505-59-3 ]
  • [ 1333507-40-6 ]
  • 5
  • [ 1018505-59-3 ]
  • [ 957120-39-7 ]
  • [ 1333509-09-3 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate;palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; for 18.0h;Inert atmosphere; Reflux; A mixture of impure 5-(4-ethylpiperazin- 1 -yl)pyridin-2-amine (1.00 g, 4.85' mmol assumed), 8-bromo-6-chloroimidazo[l ,2-a]pyridine hydrochloride salt (1.30 g, 4.85 mmol), 2,2'-bis(diphenylphosphino)-l,r-binaphthalene (634 mg, 1.02 mmol) and cesium carbonate (4.90 g, 15.0 mmol) in toluene (50 mL) was sparged with nitrogen while stirring for 10 min. Palladium(II) acetate (120 mg, 0.491 mmol) was then added and the reaction stirred at reflux for 18 h. After this time, the reaction was cooled to room temperature, diluted in a mixture of 1 : 1 methanol/methylene chloride (100 mL) and filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure and the resulting residue purified by chromatography (silica, gradient, 1 : 19 methanol/methylene chloride to 1 :6methanol/methylene chloride) to afford 6-chloro-Ar-(5-(4-ethylpiperazin-l-yl)pyiidin-2- yl)imidazo[l,2-a]pyridin-8-amine as a yellow-green solid: NMR (400 MHz, DMS0- )d 9.12 (s, 1H), 8.30 (d, J = 2.0 Hz, 1H), 8.26 (d, J = 2.0 Hz, 1H), 7.99 (d, J = 2.8 Hz, 1 H), 7.89 (d, J = 0.8 Hz, 1H), 7.55 (d, J= 0.8 Hz, 1H), 7.43 (dd, J = 8.8, 2.8 Hz, 1H), 7.35 (d, J= 8.8 Hz, 1H), 3.11-3.10 (m, 4H), 2.50-2.49 (m, 4H, merged with DMSO peak), 2.38-2.37 (m, 2H), 1.04 (t, J= 7.2 Hz, 3H).
  • 6
  • [ 1333509-07-1 ]
  • [ 1018505-59-3 ]
YieldReaction ConditionsOperation in experiment
92% With palladium 10% on activated carbon; hydrogen; In methanol; ethyl acetate; at 20℃; for 12.0h; Add to the reaction flask1-ethyl-4- (6-nitropyridin-3-yl) piperazine (0.9 g, 3.8 mmol, first step)Palladium-carbon (10%, 18 mg) and ethyl acetate / methanol (9 mL / 9 mL).In a hydrogen atmosphere, the mixture was stirred at room temperature for 12 hours.Filtered and the filtrate was concentrated to give the title compound (720 mg, yellow solid) in 92% yield.
92% With palladium on activated charcoal; hydrogen; In methanol; ethanol; at 20℃; for 2.0h; 1-ethylpiperazine (3.40g, 29.8mmol), 80 K2CO3 (4.10g, 29.6mmol), and 93 TBAI (0.42g, 1.2mmol) were added to a solution of 82 5-bromo-2-nitropyridine (4.00g, 19.7mmol) in 83 DMSO (40mL). The mixture was heated at 80C for 16h, and the reaction was poured into ice water, and extracted with DCM. The combined organic layers were washed with water, dried over anhydrous Na2SO4, concentrated under a vacuum, and purified by silica gel column chromatography (DCM/MeOH=100:1-10:1) to obtain 94 1-ethyl-4-(6-nitropyridin-3-yl)piperazine (3.59g; yield, 56%) as a yellow solid. Pd/C (0.10g) was added to the 1-ethyl-4-(6-nitropyridin-3-yl)piperazine (0.90g, 3.8mmol) in EA/MeOH (9 mL/9mL) solution. The mixture was degassed by H2, stirred at RT under a H2 atmosphere for 2h, and filtered and concentrated under a vacuum to obtain INT-2 (720.0mg; yield, 92%) as an off-white solid. ESI-MS: m/z 207.2 [M+H]+.
82% With hydrogen;palladium 10% on activated carbon; In ethanol; under 2844.39 Torr; for 2.0h; In a hydrogenation bottle, 138a (2.59 g, 10.96 mmol) , EtOH (100 mL), 10 % Pd / C (580 mg, 0.55 mmol) were added. The mixture was hydrogenated at 55 psi for 2 hrs, and then filtered through celite and washed with MeOH (20 mL). The solvent was removed in vacuo and pink solids were obtained as 138b (2.51 g, 82 ).
With hydrogen;palladium 10% on activated carbon; In ethanol; ethyl acetate; at 20℃; under 2068.65 Torr; for 1.0h;Inert atmosphere; A 500-mL Parr hydrogenation bottle was purged with nitrogen and charged with 1 - ethyl-4-(6-nitropyridin-3-yl)piperazine (1.13 g, 4.78 mmol), ethanol (60 mL), ethyl acetate (120 mL) and 10% palladium on carbon (50% wet, 480 mg dry weight). The bottle was evacuated, charged with hydrogen gas to a pressure of 40 psi and shaken for 1 h at room temperature on a Parr hydrogenation apparatus. After this time, the hydrogen gas was evacuated and nitrogen charged into the bottle. The catalyst was removed by filtration through a pad of diatomaceous earth and the filter cake washed with ethanol (10 mL). The filtrate was concentrated under reduced pressure to afford 5-(4-ethylpiperazin-l -yl)pyridin-2- amine as a light yellow solid which was used in the next step without purification: ' I i NMR (400 MHz, DMS0- )d NMR (400 MHz, DM SO 7.59 (d, J= 2.8 Hz, 1H), 7.15 (dd, J= 8.8, 2.8 Hz, 1H), 6.38 (d, J= 8.8 Hz, 1 H), 5.36 (bs, 2H), 2.93-2.91 (m, 4H), 2.50 2.49 (m, 4H, merged with DMSO peak), 2.37 (q, J= 7.2 Hz, 2H), 1.04 (t, J = 7.2 Hz, 3H).
With palladium 10% on activated carbon; hydrogen; In ethanol; ethyl acetate; at 20℃; under 2068.65 Torr; for 1.0h;Inert atmosphere; Preparation of 5-(4-ethylpiperazin-1-yl)pyridin-2-amine A 500-mL Parr hydrogenation bottle was purged with nitrogen and charged with 1-ethyl-4-(6-nitropyridin-3-yl)piperazine (1.13 g, 4.78 mmol), ethanol (60 mL), ethyl acetate (120 mL) and 10% palladium on carbon (50% wet, 480 mg dry weight). The bottle was evacuated, charged with hydrogen gas to a pressure of 40 psi and shaken for 1 h at room temperature on a Parr hydrogenation apparatus. After this time, the hydrogen gas was evacuated and nitrogen charged into the bottle. The catalyst was removed by filtration through a pad of diatomaceous earth and the filter cake washed with ethanol (10 mL). The filtrate was concentrated under reduced pressure to afford 5-(4-ethylpiperazin-1-yl)pyridin-2-amine as a light yellow solid which was used in the next step without purification: 1H NMR (400 MHz, DMSO-d6.) d 1H NMR (400 MHz, DMSO-d6.) d 7.59 (d, J=2.8 Hz, 1H), 7.15 (dd, J=8.8, 2.8 Hz, 1H), 6.38 (d, J=8.8 Hz, 1H), 5.36 (bs, 2H), 2.93-2.91 (m, 4H), 2.50-2.49 (m, 4H, merged with DMSO peak), 2.37 (q, J=7.2 Hz, 2H), 1.04 (t, J=7.2 Hz, 3H).
With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; for 12.0h; 650 mg (2.13 mmol) of 1-ethyl-4-(6-nitropyridin-3-yl)piperazine prepared in Step 1 was dissolved in 45 ml of methanol,10% palladium carbon (250 mg, cat) was added, the atmosphere was replaced three times with hydrogen gas, and thereaction was carried out at room temperature for 12h in the atmosphere of hydrogen gas under 3 atmos. After the reactionstopped, the reaction product was filtered with a small amount of diatomite, and the filter cake was washed once with20 ml of a mixed solvent of dichloromethane and methanol (V/V = 10:1). Then, the filtrate was collected and concentratedunder reduced pressure to give 559 mg of crude product of the titled compound (transparent and viscous material) whichwas used in the subsequent reaction directly without further purification. MS (ESI): m/z 207.1 [M+H]+.
With palladium on activated charcoal; hydrogen; In methanol; To a solution of compound 90 ( 1.5 g, 6.4 mmol) in MeOH (20mL) was added Pd/C (0.5 g). The mixture was stirred under H2 atmosphere overnight. After LCMS indicated completion, the mixture was filtered, washed with MeOH, the filtrate was concentrated to afford the crude product (1.3 g, crude) which was used to the next step directly. *H NMR (300 MHz, CDCb): delta 7.79 (s, 1 H), 7.23-7.20 (m, 1 H), 6.52-6.49 (m, 1 H), 4.25 (br, 2 H), 3.16- 3.14 (m, 4 H), 2.74-2.57 (m, 4 H), 2.32-2.28 (m, 2 H), 1.21 (t, J= 7.2 Hz, 3 H).

  • 7
  • [ 1018505-59-3 ]
  • [ 1333507-26-8 ]
  • 8
  • [ 14529-54-5 ]
  • [ 1018505-59-3 ]
  • [ 1346673-43-5 ]
YieldReaction ConditionsOperation in experiment
57% With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; To a round-bottomed flask equipped with a stirring bar, 138b (2.52 g, 12.22 mmol), 3,5-dibromo-l-methylpyridin-2(lH)-one (4.89 g, 18.32 mmol), Pd2(dba)3 (1.12 g, 1.22 mmol), XantPhos (1.13 mg, 1.96 mmol), Cs2CC>3 (13.14 g, 40.33 mmol) and dioxane (50 mL) were added. The reaction mixture was heated at 100 C overnight. CH2C12 (200 mL) was added to the resulting mixture was washed with water (30 mL X 3). CH2C12 (200 mL) was added and the resulting mixture was washed with water (30 mL X 3), brine (30 mL X 1), dried over MgS04, filtered, and removed solvent in vacuo. CH2C12 / ether (1 :2, 5 mL) was added followed by sonication, the precipitation was filtered as 138c, a yellow solid, 2.718 g (57 %).
  • 9
  • [ 1018505-59-3 ]
  • [ 1346673-44-6 ]
  • 10
  • [ 1018505-59-3 ]
  • [ 1346669-87-1 ]
  • 11
  • [ 1178884-53-1 ]
  • [ 1018505-59-3 ]
  • [ 1360055-69-1 ]
  • 12
  • [ 1178884-53-1 ]
  • [ 1018505-59-3 ]
  • [ 1360057-20-0 ]
YieldReaction ConditionsOperation in experiment
44% With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 18.0h;Inert atmosphere; A solution of <strong>[1018505-59-3]5-(4-ethylpiperazin-1-yl)pyridin-2-amine</strong> (185 mg, 0.90 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (200 mg, 0.90 mmol) cesium carbonate (1.02 g, 3.13 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethlxanthene (77.7 mg, 0.13 mmol) in dioxane (10 ml) was flushed with argon before tris(dibenzylideneacetone)dipalladium(0) (61.5 mg, 0.07 mmol) was added and the resulting solution was heated at 90 C. for 18 h. The mixture was cooled to room temperature and diluted with dichloromethane and water. The layers were separated and the aqueous layer was extracted with dichloromethane (2*25 mL). The organic layers were combined, dried over magnesium sulfate. The resulting mixture was filtered and concentrated in vacuo. The residue was triturated with methanol and dichloromethane and filtered, washed with ether and dried to give 6-chloro-4-[5-(4-ethyl-piperazin-1-yl)-pyridin-2-ylamino]-2-methyl-2H-pyridazin-3-one (138 mg, 44%) as a yellow solid.
YieldReaction ConditionsOperation in experiment
With palladium 10% on activated carbon; hydrogen; In methanol; for 12.0h; General procedure: A solution of l-methyl-4-(6-nitro-pyridin-3-yl) piperazine (1.5 g, 6.83 mmol) in MeOH (75 mL) was hydrogenated in the presence of 10% Pd/C (0.3 g) using an H2 balloon. After 12 h, the reaction mixture was filtered through a pad of Celite and rinsed with MeOH (2 x 15 mL). The filtrate was concentrated and purified by triturating in n-pentane to afford the title compound (1.0 g) as a brown solid. 1H NMR (400 MHz, CDC13) delta 7.78 (d, J = 2.6 Hz, 1H), 7.18 (dd, J = 8.8, 2.9 Hz, 1H), 6.49 (dd, J= 8.8, 0.6 Hz, 1H), 3.10 - 3.03 (m, 4H), 2.59 (dd, J= 11.9, 6.9 Hz, 4H), 2.35 (s, 3H).
  • 14
  • [ 1018505-59-3 ]
  • [ 1585145-78-3 ]
  • [ 1585145-49-8 ]
YieldReaction ConditionsOperation in experiment
600 mg With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos; In toluene; tert-butyl alcohol; at 120℃;Inert atmosphere; To a solution of 3-chloro-7-(2, 6-dichloro-3, 5-dimethoxyphenyl) isoqinoline (600 mg, 1.628 mmol), 5-(4-ethylpiprazine-l-yl) pyridine-2-amine (step 3.1) (376 mg, 1.82 mmol), X-Phos (77.60 mg, 10 mol %) and cesium carbonate (1.06 g, 1.25 mmol) in Toluene (15 mL) and t- BuOH (5 mL) (4: 1) argon was purged for 20 min. Then was added Pd2 (dba)3 (149 mg, 10 mol %) again argon was purged for 5 min. The reaction mixture was heated at 120C overnight. The reaction mixture was cooled to room temperature and filtered through celite pad and filtrate was concentrated under reduced pressure. Product was purified by column chromatography on silica gel column using DCM: MeOH: NH3 aq. (95:5: 1%) as an eluent to afford 7-(2, 6-dichloro-3, 5-dimethoxyphenyl)-N-[5-(4-ethylpiperazin-l-yl) pyridin-2-yl] isoquinoline-3 -amine (600 mg) as a pale yellow solid. 1H NMR (400 MHz, CDC13) delta 8.97 (s, 1H), 8.09 (dd, J = 25.7, 7.3 Hz, 2H), 7.82 - 7.68 (m, 2H), 7.41 (dd, J = 8.5, 1.6 Hz, 1H), 7.32 (dd, J = 8.9, 2.9 Hz, 1H), 7.17 - 7.10 (m, 1H), 6.65 (s, 1H), 3.99(s, 6H), 3.26 - 3.16 (m, 4H), 2.71 - 2.62 (m, 4H), 2.51 (q, J = 7.2 Hz, 2H), 1.15 (t, J= 7.2 Hz, 3H). M/Z: 537.1, M+l : 538.6, tR= 0.81 min. (System 1)
  • 15
  • [ 1018505-59-3 ]
  • [ 1585145-77-2 ]
  • [ 1585145-46-5 ]
YieldReaction ConditionsOperation in experiment
20 mg With palladium diacetate; caesium carbonate; XPhos; In toluene; tert-butyl alcohol; at 120℃;Inert atmosphere; To a solution of 3-chloro-7-(3, 5-dimethoxyphenyl) isoqinoline (50 mg, 0.167 mmol) , 5-(4- ethylpiprazine-l-yl) pyridine-2-amine (38 mg , 0.183 mmol), X-Phos ( 8 mg, 10 mol% ) and cesium carbonate (108.4 mg, 0.334 mmol) in Toluene (4 mL) and t-BuOH (1 mL) (4: 1) argon was purged for 20 min. Then was added Pd(OAc)2 (3.76 mg, 10 mol%) again argon was purged for 5 min. The reaction mixture was heated at 120C for O/N. The reaction mixture was cooled to room temperature and filtered through celite pad and filtrate was concentrated under reduced pressure. Product was purified by column chromatography on silica gel column using DCM: MeOH: NH3 aq. (94:6: 1%) as an eluent to afford 7-(3,5-dimethoxyphenyl)-N-[5- (4-ethylpiperazin-l-yl)pyridin-2-yl]isoquinolin-3 -amine (20 mg) as a brown solid. 1H NMR (400 MHz, CDC13) delta 9.00 (s, 1H), 8.14 (s, 1H), 8.06 (d, J = 2.5 Hz, 1H), 8.00 (s, 1H), 7.79 (dd, J = 19.3, 8.6 Hz, 2H), 7.42 (s, 1H), 7.31 (dd, J = 8.9, 2.7 Hz, 1H), 7.10 (d, J = 8.9 Hz, 1H), 6.83 (d, J = 1.9 Hz, 2H), 6.49 (s, 1H), 3.88 (s, 6H), 3.25 - 3.14 (m, 4H), 2.66 (d, J = 4.4 Hz, 4H), 2.50 (q, J = 7.1 Hz, 2H), 1.15 (t, J = 7.2 Hz, 3H).M/Z: 469.58, M+l : 470.4, tR= 2.1 min. (System 2)
  • 16
  • [ 1018505-59-3 ]
  • 8-bromo-6-chloroimidazo[1,2-a]pyridine hydrochloride [ No CAS ]
  • [ 1333509-09-3 ]
YieldReaction ConditionsOperation in experiment
With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; for 18.0h;Inert atmosphere; Reflux; Preparation of 6-chloro-N-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)imidazo[1,2-a]pyridin-8-amine A mixture of impure <strong>[1018505-59-3]5-(4-ethylpiperazin-1-yl)pyridin-2-amine</strong> (1.00 g, 4.85 mmol assumed), 8-bromo-6-chloroimidazo[1,2-a]pyridine hydrochloride salt (1.30 g, 4.85 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (634 mg, 1.02 mmol) and cesium carbonate (4.90 g, 15.0 mmol) in toluene (50 mL) was sparged with nitrogen while stirring for 10 min. Palladium(II) acetate (120 mg, 0.491 mmol) was then added and the reaction stirred at reflux for 18 h. After this time, the reaction was cooled to room temperature, diluted in a mixture of 1:1 methanol/methylene chloride (100 mL) and filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure and the resulting residue purified by chromatography (silica, gradient, 1:19 methanol/methylene chloride to 1:6 methanol/methylene chloride) to afford 6-chloro-N-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)imidazo[1,2-a]pyridin-8-amine as a yellow-green solid: 1H NMR (400 MHz, DMSO-d6.) d 9.12 (s, 1H), 8.30 (d, J=2.0 Hz, 1H), 8.26 (d, J=2.0 Hz, 1H), 7.99 (d, J=2.8 Hz, 1H), 7.89 (d, J=0.8 Hz, 1H), 7.55 (d, J=0.8 Hz, 1H), 7.43 (dd, J=8.8, 2.8 Hz, 1H), 7.35 (d, J=8.8 Hz, 1H), 3.11-3.10 (m, 4H), 2.50-2.49 (m, 4H, merged with DMSO peak), 2.38-2.37 (m, 2H), 1.04 (t, J=7.2 Hz, 3H).
  • 17
  • [ 1018505-59-3 ]
  • N-cyclopentyl-5-(2-((5-(4-ethylpiperazin-1-yl)pyridin-2-yl)-amino)pyrimidin-4-yl)-4-methylthiazol-2-amine [ No CAS ]
  • 18
  • [ 1018505-59-3 ]
  • N-cyclopentyl-5-(2-((5-(4-ethylpiperazin-1-yl)pyridin-2-yl)amino)-5-fluoropyrimidin-4-yl)-4-methylthiazol-2-amine [ No CAS ]
  • 19
  • [ 1018505-59-3 ]
  • 1-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)guanidine trifluoroacetate [ No CAS ]
  • 20
  • [ 1018505-59-3 ]
  • [ 322474-21-5 ]
  • 1-ethyl-4-(6-(2,3-bis(tert-butoxycarbonyl)guanidino)pyridin-3-yl)piperazine [ No CAS ]
  • 21
  • [ 1018505-59-3 ]
  • 7-(2-chloro-5-fluoropyrimidin-4-yl)-5-fluoro-1,1-dimethyl-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole [ No CAS ]
  • N-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)-5-fluoro-4-(5-fluoro-1,1-dimethyl-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-7-yl)pyrimidin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
17% 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 120℃; for 12.0h; Add to the reaction flask7- (2-chloro)Fluoro-pyrimidin-4-yl) -5-fluoro-2,3-dihydro-1H-benzo [d]Pyrrole [1,2-a] imidazole(200 mg, 0.6 mmol, prepared according to the procedure of Example 1)5- (4-ethylpiperazin-1-yl) pyridin-2-amine (123 mg, 0.6 mmol, prepared in second step)Cesium carbonate (390 mg, 1.2 mmol), Pd2 (dba) 3 (55 mg, 0.06 mmol)XantPhos (35 mg, 0.06 mmol) and anhydrous 1,4-dioxane (5 mL).The mixture was stirred at 120 C for 12 hours.Cooled to room temperature, water (10 mL) and ethyl acetate (20 mL x 3) were added to the solution.The combined organic phases were washed with saturated sodium chloride solution (20 mL), dried over anhydrous sodium sulfate,Filtered, concentrated under reduced pressure. The residue was purified by column chromatography (DCM / MeOH = 10: 1)The resulting residue was purified to give the title compound (50 mg, white solid)Yield 17%.
17 mg 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℃; for 2.08333h;Inert atmosphere; Nitrogen was bubbled into a solution of compound 91 (65 mg, 0.3 mmol, 1 eq), Compound 14 (100 mg, 0.3 mmol, 1 eq; see Example 1), Pd2(dba)3 (27 mg, 0.03 mmol, 0.1 eq), Xantphos (36.3 mg, 0.063 mmol, 0.21 eq) and Cs2C03(195 mg, 0.6 mmol, 2 eq) in dioxane (28 mL) for 5 min. And then the mixture was stirred at 110 C for 2h. After completion, the mixture was cooled down to rt, diluted with DCM (50 mL) and filtered through Celite, rinsed with DCM (20 mL), dried over sodium sulfate, concentrated and purified by pre-HPLC to give the desired product (17 mg, 7%) as a white solid. NMR (300 MHz, CDC ): delta 8.41-8.40 (m, 1 H), 8.31 (d, J= 9 Hz, 1 H), 8.09-8.06 (m, 3 H), 7.82 (d, J= 11.7 Hz, 1 H), 7.38-7.34 (m, 1 H), 3.28-3.26 (m, 4 H), 3.19-3.14 (m, 2 H), 2.76-2.74 (m, 4 H), 2.63- 2.58 (m, 4 H), 1.74 (s, 6 H), 1.26-1.20 (m, 3 H). LCMS: (M+H)+ = 504.8. HPLC: 96.3%.
  • 22
  • [ 1018505-59-3 ]
  • 5-(2-chloro-5-fluoropyrimidin-4-yl)-3-ethyl-7-fluoro-2,3-dimethyl-3H-indole [ No CAS ]
  • 4-(3-ethyl-7-fluoro-2,3-dimethyl-3H-indol-5-yl)-N-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)-5-fluoropyrimidin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
10% With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 150℃; for 1.0h; General procedure: Pd2(dba)3 (86.4mg, 0.09mmol) and Xant-phos (109.2mg, 0.19mmol) were added under N2 to a solution of 154 1E (290.0mg, 0.94mmol), INT-7 (228.6mg, 1.04mmol), and 152 potassium phosphate (400.5mg, 1.88mmol) in 111 1,4-dioxane (10mL). Then the mixture was reacted in the microwave at 150C for 1h. The mixture was cooled to RT, filtered, diluted with water (10mL), and extracted with DCM (10mL×3). The combined organic layers were washed with brine (30mL), dried over anhydrous Na2SO4, concentrated under a vacuum, and purified by preparative thin-layer chromatography to obtain 157 compound 1 (140.3mg; yield, 30%) as a yellow solid.
  • 23
  • [ 1018505-59-3 ]
  • 5’-(2-chloro-5-fluoropyrimidin-4-yl)-7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole] [ No CAS ]
  • N-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)-5-fluoro-4-(7'-fluoro-2'-methylspiro[cyclopentane-1,3'-indol]-5'-yl)pyrimidin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 150℃; for 1.0h; General procedure: Pd2(dba)3 (86.4mg, 0.09mmol) and Xant-phos (109.2mg, 0.19mmol) were added under N2 to a solution of 154 1E (290.0mg, 0.94mmol), INT-7 (228.6mg, 1.04mmol), and 152 potassium phosphate (400.5mg, 1.88mmol) in 111 1,4-dioxane (10mL). Then the mixture was reacted in the microwave at 150C for 1h. The mixture was cooled to RT, filtered, diluted with water (10mL), and extracted with DCM (10mL×3). The combined organic layers were washed with brine (30mL), dried over anhydrous Na2SO4, concentrated under a vacuum, and purified by preparative thin-layer chromatography to obtain 157 compound 1 (140.3mg; yield, 30%) as a yellow solid.
  • 24
  • [ 1018505-59-3 ]
  • 5'-(2-chloro-5-fluoropyrimidin-4-yl)-2'-methylspiro[cyclopentane-1,3'-indole] [ No CAS ]
  • N-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)-5-fluoro-4-(2'-methylspiro[cyclopentane-1,3'-indol]-5'-yl)pyrimidine-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
20% With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 150℃; for 1.0h; General procedure: Pd2(dba)3 (86.4mg, 0.09mmol) and Xant-phos (109.2mg, 0.19mmol) were added under N2 to a solution of 154 1E (290.0mg, 0.94mmol), INT-7 (228.6mg, 1.04mmol), and 152 potassium phosphate (400.5mg, 1.88mmol) in 111 1,4-dioxane (10mL). Then the mixture was reacted in the microwave at 150C for 1h. The mixture was cooled to RT, filtered, diluted with water (10mL), and extracted with DCM (10mL×3). The combined organic layers were washed with brine (30mL), dried over anhydrous Na2SO4, concentrated under a vacuum, and purified by preparative thin-layer chromatography to obtain 157 compound 1 (140.3mg; yield, 30%) as a yellow solid.
  • 25
  • [ 1018505-59-3 ]
  • 5-(2-chloro-5-fluoropyrimidin-4-yl)-3-ethyl-2,3-dimethyl-3H-indole [ No CAS ]
  • 4-(3-ethyl-2,3-dimethyl-3H-indol-5-yl)-N-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)-5-fluoropyrimidine-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
19% With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 150℃; for 1.0h; General procedure: Pd2(dba)3 (86.4mg, 0.09mmol) and Xant-phos (109.2mg, 0.19mmol) were added under N2 to a solution of 154 1E (290.0mg, 0.94mmol), INT-7 (228.6mg, 1.04mmol), and 152 potassium phosphate (400.5mg, 1.88mmol) in 111 1,4-dioxane (10mL). Then the mixture was reacted in the microwave at 150C for 1h. The mixture was cooled to RT, filtered, diluted with water (10mL), and extracted with DCM (10mL×3). The combined organic layers were washed with brine (30mL), dried over anhydrous Na2SO4, concentrated under a vacuum, and purified by preparative thin-layer chromatography to obtain 157 compound 1 (140.3mg; yield, 30%) as a yellow solid.
  • 26
  • [ 1018505-59-3 ]
  • 1-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)guanidine [ No CAS ]
  • 27
  • [ 1018505-59-3 ]
  • 5-(2-chloro-5-fluoropyrimidin-4-yl)-3-ethyl-7-fluoro-2,3-dimethyl-3H-indole [ No CAS ]
  • 4-(3-ethyl-7-fluoro-2,3-dimethyl-3H-indol-5-yl)-N-(5-(4-ethylpiperazin-1-yl)pyridin-2-yl)-5-fluoropyrimidine-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
10% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; diphenylphosphane; In 1,4-dioxane; at 120℃; for 1.0h;Microwave irradiation; A reaction flask was charged with 321 mg (1 mmol) of 5-(2-chloro-5-fluoropyrimidin-4-yl)-3-ethyl-7-fluoro-2,3-dimethyl-3H-indole prepared in Step 3, 206 mg (1 mmol) of 5-(4-ethylpiperazin-1-yl)pyridin-2-amino obtained in Step 2, 2 ml of 1,4-dioxane, 650 mg (2 mmol) of Cs2CO3, 91mg (0.1mmol) of Pd2(dba)3, and 58mg (0.1mmol) of diphenylphosphine. The mixture was heated to 120C to conduct microwave reaction for 1 h. The reaction product was cooled to room temperature, added with 10ml of water and then extracted with ethyl acetate three times (40ml for each time). The organic phases were combined, washed once with 40 ml of saturated salt solution, dried with sodium sulfate, filtered, concentrated under reduced pressure and separated by silica gel column chromatography (DCM/MeOH = 10:1) to give the titled compound (49 mg, yellow solid), yield 10%. 1H-NMR(400MHz, CDCl3) delta9.25(br s, 1H), 8.46(d, 1H, J=3.2Hz), 8.28(d, 1H, J=9.2Hz), 8.17(d, 1H, J=2.0Hz), 7.90(d, 1H, J=11.2Hz), 7.82(s, 1H), 7.35(dd, 1H, J=9.2Hz, 2.8Hz), 3.20-3.18(m, 4H), 2.64-2.61(m, 4H), 2.51(q, 2H, J=6.8Hz), 2.31(s, 3H), 2.03-1.94(m, 1H), 1.89-1.82(m, 1H), 1.36(s, 3H), 1.13(t, 3H, J=7.2Hz), 0.48(t, 3H, J=7.2Hz). MS(ESI):m/z 492.3[M+H]+.
  • 28
  • [ 1018505-59-3 ]
  • 4-(6-chloro-3-fluoro-pyrazin-2-ylamino)pyrimidine-2-carboxylic acid [ No CAS ]
  • 4-(6-chloro-3-fluoro-pyrazin-2-yl-amino)-pyrimidine-2-amido-[5-(4-ethyl-piperazin-1-yl)]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 16.0h; The 4 - (2 - chloro -3 - fluoro - pyrazine amino) -2 - pyrimidine formic acid (1.35 g 1.2 eq), 5 - (4 - ethyl - piperazine -1 - yl) - piperidine -2 - amino (0.81 g 1 eq) and triethylamine (500 mul) in DMF (15 ml) in, then added HBTU (1.51 g 1.5 eq). The mixture stirring at room temperature to 16 hours, then EtOAc (50 ml) and saturated NaHCO3Solution (15 ml), and for separating each layer of EtOAc (2 × 15 ml) extraction the aqueous layer, the combined organic layer dried (MgSO4), filtering and evaporation to dryness, the residue through the column chromatography purification, and to obtain white solid compound of 1.42 g (yield: 62%).
62% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 16.0h; 4-(2-Chloro-3-fluoro-pyrazinylamino)-2-pyrimidinecarboxylic acid (1.35 g, 1.2 eq),5-(4-Ethyl-piperazin-1-yl)-piperidin-2-amino (0.81 g, 1 eq) and triethylamine (500 muL)In DMF (15 mL) followed by HBTU (1.51 g, 1.5 eq).The mixture was stirred at room temperature for 16 hours.Then EtOAc (50 mL) and saturated NaHCO3 (15 mL)The layers were separated and the aqueous layer was extracted with EtOAc EtOAcThe combined organic layers were dried (MgSO4), filtered and evaporated.The residue was purified by column chromatography.1.42 g of the target compound 2 was obtained as a white solid(yield: 62%),Its nuclear magnetic resonance spectrum data is as follows:
  • 29
  • [ 1018505-59-3 ]
  • 4-(2-dimethylcarbonyl-2-carbonylethylamino)-2-pyrimidinecarboxylic acid [ No CAS ]
  • 4-(2-dimethylcarbamoyl-2-oxo-ethylamino)-pyrimidine-2-amido-[5-(4-ethyl-piperazin-1-yl)]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 16.0h; The 4 - (2 - dimethyl carbonyl -2 - carbonyl - ethylamine) -2 - pyrimidine formic acid (1.26 g 1.2 eq), 5 - (4 - ethyl - piperazine -1 - yl) - piperidine -2 - amino (0.81 g 1 eq) and triethylamine (500 mul) in DMF (15 ml) in, then added HBTU (1.51 g 1.5 eq). The mixture stirring at room temperature to 16 hours, then EtOAc (50 ml) and saturated NaHCO3Solution (15 ml), and for separating each layer of EtOAc (2 × 15 ml) extraction the aqueous layer, the combined organic layer drying (MgSO4), Filtering and evaporation to dryness, the residue through the column chromatography purification, and to obtain white solid compound of 1.04 g (yield: 47%).
47% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 16.0h; 4-(2-Dimethylcarbonyl-2-carbonyl-ethylamino)-2-pyrimidinecarboxylic acid (1.26 g, 1.2 eq),5-(4-Ethyl-piperazin-1-yl)-piperidin-2-amino (0.81 g, 1 eq)And triethylamine (500 muL) in DMF (15 mL),Then HBTU (1.51 g, 1.5 eq) was added. The mixture was stirred at room temperature for 16 hours.Then with EtOAc (50 mL)And saturated NaHCO3 solution(15 mL), the layers were separated and EtOAc EtOAcThe combined organic layers were dried (MgSO4), filtered and evaporated.The residue was purified by column chromatography.1.04 g of the title compound 6 was obtained as a white solid(yield: 47%),Its nuclear magnetic resonance spectrum data is as follows:
Same Skeleton Products
Historical Records

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