Home Cart 0 Sign in  

[ CAS No. 1876467-74-1 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 1876467-74-1
Chemical Structure| 1876467-74-1
Structure of 1876467-74-1 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 1876467-74-1 ]

Related Doc. of [ 1876467-74-1 ]

Alternatived Products of [ 1876467-74-1 ]

Product Details of [ 1876467-74-1 ]

CAS No. :1876467-74-1 MDL No. :MFCD31561442
Formula : C20H21N7O Boiling Point : -
Linear Structure Formula :- InChI Key :YBXRSCXGRPSTMW-CYBMUJFWSA-N
M.W : 375.43 Pubchem ID :118869362
Synonyms :
BAY-1895344

Calculated chemistry of [ 1876467-74-1 ]

Physicochemical Properties

Num. heavy atoms : 28
Num. arom. heavy atoms : 20
Fraction Csp3 : 0.3
Num. rotatable bonds : 3
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 110.14
TPSA : 84.75 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -7.45 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.32
Log Po/w (XLOGP3) : 1.6
Log Po/w (WLOGP) : 2.26
Log Po/w (MLOGP) : 0.73
Log Po/w (SILICOS-IT) : 2.32
Consensus Log Po/w : 1.85

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.51
Solubility : 0.117 mg/ml ; 0.000312 mol/l
Class : Soluble
Log S (Ali) : -2.99
Solubility : 0.383 mg/ml ; 0.00102 mol/l
Class : Soluble
Log S (SILICOS-IT) : -5.88
Solubility : 0.000489 mg/ml ; 0.0000013 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.64

Safety of [ 1876467-74-1 ]

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

Application In Synthesis of [ 1876467-74-1 ]

* 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 [ 1876467-74-1 ]

[ 1876467-74-1 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 74572-04-6 ]
  • [ 1876467-74-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: potassium carbonate / dichloromethane / 0.5 h / 20 °C 1.2: 18 h / 20 °C 2.1: trichlorophosphate / 1,2-dichloro-ethane / 0.5 h / 0 - 20 °C / Inert atmosphere 2.2: 20 - 80 °C 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere 4.1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 16 h / 90 °C / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C / Inert atmosphere 6.1: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 0.33 h / 130 °C / Microwave irradiation 6.2: 3 h / 20 °C
Multi-step reaction with 7 steps 1.1: potassium carbonate / dichloromethane / 0.5 h / 20 °C 1.2: 18 h / 20 °C 2.1: trichlorophosphate / 1,2-dichloro-ethane / 0.5 h / 20 °C / Inert atmosphere 2.2: 20 - 80 °C / Inert atmosphere 3.1: lithium hexamethyldisilazane / N,N-dimethyl-formamide; tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere 4.1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 16 h / 90 °C / Inert atmosphere; Microwave irradiation 5.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C / Inert atmosphere 6.1: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / water; 1,2-dimethoxyethane / 0.33 h / 130 °C / Microwave irradiation 7.1: sulfuric acid / 3 h / 20 °C
  • 2
  • [ 1257237-31-2 ]
  • [ 1876467-74-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: trichlorophosphate / 1,2-dichloro-ethane / 0.5 h / 0 - 20 °C / Inert atmosphere 1.2: 20 - 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere 3.1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 16 h / 90 °C / Inert atmosphere 4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C / Inert atmosphere 5.1: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 0.33 h / 130 °C / Microwave irradiation 5.2: 3 h / 20 °C
Multi-step reaction with 6 steps 1.1: trichlorophosphate / 1,2-dichloro-ethane / 0.5 h / 20 °C / Inert atmosphere 1.2: 20 - 80 °C / Inert atmosphere 2.1: lithium hexamethyldisilazane / N,N-dimethyl-formamide; tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere 3.1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 16 h / 90 °C / Inert atmosphere; Microwave irradiation 4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C / Inert atmosphere 5.1: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / water; 1,2-dimethoxyethane / 0.33 h / 130 °C / Microwave irradiation 6.1: sulfuric acid / 3 h / 20 °C
  • 3
  • [ 1876471-17-8 ]
  • [ 1876467-74-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere 2.1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 16 h / 90 °C / Inert atmosphere 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C / Inert atmosphere 4.1: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 0.33 h / 130 °C / Microwave irradiation 4.2: 3 h / 20 °C
  • 4
  • [ 1876471-18-9 ]
  • [ 1876467-74-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 16 h / 90 °C / Inert atmosphere 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C / Inert atmosphere 3.1: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 0.33 h / 130 °C / Microwave irradiation 3.2: 3 h / 20 °C
Multi-step reaction with 4 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 16 h / 90 °C / Inert atmosphere; Microwave irradiation 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C / Inert atmosphere 3: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / water; 1,2-dimethoxyethane / 0.33 h / 130 °C / Microwave irradiation 4: sulfuric acid / 3 h / 20 °C
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 0.25 h / 0 - 10 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium hydrogencarbonate / Isopropyl acetate; water / 2.5 h / 50 °C 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; ethyl acetate / 1 h / 65 °C 4: hydrogenchloride; water / dichloromethane; methanol / 0.17 h / 0 - 22 °C / Large scale
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium hydrogencarbonate / Isopropyl acetate; water / 2.5 h / 50 °C 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; ethyl acetate / 1 h / 65 °C 4: hydrogenchloride; water / dichloromethane; methanol / 0.17 h / 0 - 22 °C / Large scale

  • 5
  • [ 1876471-20-3 ]
  • [ 1876467-74-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C / Inert atmosphere 2.1: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 0.33 h / 130 °C / Microwave irradiation 2.2: 3 h / 20 °C
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C / Inert atmosphere 2: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / water; 1,2-dimethoxyethane / 0.33 h / 130 °C / Microwave irradiation 3: sulfuric acid / 3 h / 20 °C
  • 6
  • 2-[(3R)-3-methylmorpholin-4-yl]-8-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-1,7-naphthyridin-4-yl trifluoromethanesulfonate [ No CAS ]
  • [ 847818-74-0 ]
  • 2-[(3R)-3-methylmorpholin-4-yl]-4-(1-methyl-1H-pyrazol-5-yl)-8-(1H-pyrazol-5-yl)-1,7-naphthyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% I nte rmed iate-10 (0.5 g, 0.95 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl )-1H-pyrazole (415 mg, 1.9 mmol), aq. potassium carbonate (1.4 ml, 2 M) and PdCI2(PPh3)2 (67 mg,0.094 mmol) were solubilised in dimethoxyethane (60 ml). The reaction mixture was stirred for 20minutes at 130°C under microwave irradiation. After cooling to rt, the reaction mixture wasfiltered through a silicon filter and concentrated under reduced pressure. The crude material waspurified by flash column chromatography (hexane/ethyl acetate/ethanol mixture). The desiredfractions were concentrated under reduced pressure and solubilised in conc. sulphuric acid (5 ml).The mixture was stirred for 3h at rt. The mixture was then poured into ice and basified using solidsodium hydrogen carbonate. The suspension was filtered and the solid was stirred with ethanol at40°C, filtered and dried under reduced pressure. The title compound was obtained in 78percent yield(0.28 g).?H-NMR (400MHz, DMSO-d5): 6 [ppm]= 1.30 (d, 3H), 3.30 - 3.40 (m, 1H), 3.51 - 3.62 (m, 1H), 3.68 -3.77 (m, 4H), 3.79 - 3.86 (m, 1H), 4.01 - 4.09 (m, 1H), 4.18 - 4.28 (m, 1H), 4.60 -4.69 (m, 1H), 6.59 (d, 1H), 7.27 (d, 1H), 7.42 (s, 1H), 7.60 (s, 1H), 7.63 -7.69 (m, 2H), 8.35 (d, 1H), 13.42 (br. s, 1H).
  • 7
  • [ 2243206-56-4 ]
  • [ 1876467-74-1 ]
YieldReaction ConditionsOperation in experiment
70.25% With hydrogenchloride; water In methanol; dichloromethane at 0 - 22℃; for 0.166667h; Large scale; 1 d; 2 c; 2 d; 4 c; 5; 6 The principal is described for a divided batch of 17.8 kg (Vllc/Vlld) in dichloromethane. 17.8 kg of (Vllc/Vlld) in dichloromethane was taken from a barrel and the barrel was washed with 800 g dichloromethane. Then 9 L dichloromethane were distilled off at normal pressure (600). The solution was cooled to 220 and 3.3 kg dichloromethane and 7.2 kg methanol were added. The mixture was cooled to 0-50 and 16. 8 kg of aqueous hydrochloric acid solution were added, keeping the temperature between 0-20. The mixture was stirred for 10 min at 20-22. Phases were separated and the water phase was extracted two times with each 8.8 kg dichloromethane. The water phase was separated and 800 g N-acetyl cysteine was added, the solution was stirred for 12 h at 20°C. Then 17.6 kg dichloromethane were added and 8246 g of an aqueous 5N potassium hydroxide solution were added and the mixture stirred for 30 min. The final pH of the aqueous phase was pH = 13.6 (at this point the pH has to be 12-14). The phases were separated, the water phase extracted with 5.2 kg dichloromethane and the organic phases combined. 22.7 kg of compound (I) in dichloromethane were obtained.The following table summarizes the result of 6 batches prepared in the described manner:For the next process step two times 3 batches of the previous prepared batches were combined and converted into the final product:Solvent switch dichloromethane to n-butanol: 23.9 kg, 23.6 kg and 23.0 kg of compound (I) were combined (total 70.5 kg + 5.0 kg for washing ) and were slowly added to a 16.6 kg n- butanol which was preheated to 98. 59 liter dichl oromethane were distilled off at normal pressure. The inner temperature during distillation was 81 to 90. Then 5.0 kg dichloromethane which was used to clean the pipes were also distilled off (5 liter). 15.5 kg n butanol were added and 10 I were distilled off at normal pressure (88 to 930). The temperature was increased to 1080 (inner temperatu re, 100 ml n-butanol distilled off). This is the point, where no dichloromethane is left. The solution is cooled to 20-220 (over 7 h (ramp)). The suspension is stirred for 1 h at 200, then cooled down to 2-30, stirred for 1 h at this temperature. The crystals were isolated by filtration and were washed with 8.0 kg cold n- butanol. The wet filter cake containing the product (I) was dissolved directly from the filter (without isolation) using 47.5 kg of 300 warm dich loromethane (in the case that this amount is not enough, more dichloromethane could be used and later distilled off). The solution was cooled to 200 and 1020 g of Quadrasil Mercaptoprop yl (Pd scavenger from Johnson Matthey, CAS Number 1225327-73-0) and 1020 g of Isolute Si-TMT (the silica bound equivalent of 2,4,6-trimercaptotriazine (TMT), a Pd scavenger from Biotage AB, Sweden, Part No. 9538- 1000) were added. The suspension was stirred for 12 h at 20-210. The suspension was filtered and the filter cake was washed two times with each 13.3 kg dichloromethane. The filtrate was filtered again (GMP particle filtration).Final crystallization processSolvent switch form dichloromethane to n-butanol: the filtrate of compound (I) was slowly added to a 16.5 kg n-butanol which was preheated to 980. 53 liter dichloromethane were distilled off at normal pressure. The inner temperature during distillation was 93 to 980. Then 5.0 kg dichloromethane which was used to clean the pipes were also distilled off (4 liter). 9.0 kg n-butanol was added and 10,5 I were distilled off at normal pressure (90 to 910). The temperature was increased to 1090 (inner temperatu re, 100 ml n-butanol distilled off). This is the point, where no dichloromethane is left. The solution is cooled to 20-220 (over 7 h (ramp)). The suspension is stirred for 1 h at 200, then cooled down to 2-30, stirred for 1 h at this temperature. The crystals were isolated by filtration and were washed with 8.0 kg cold n- butanol. The product was dried under vacuum (30 mbar) at 500 for at least 12 h (until constant weight).3.753 kg (67% th.) of yellow crystals were obtained.Yield calculation: from 3 times 3.4 kg (IXb) = 10.2 kg : 7.819 kg of desired product (I) in 70.25% th. yield were obtained:
51% With hydrogenchloride In methanol; water at 20℃; for 1h; 1.b; 2c Preparation of 2-[(3R)-3-methylmorpholin-4-yl]-4-(1-methyl-1H-pyrazol-5-yl)-8-(1H-pyrazol-5-yl)-1,7-naphthyridine-Form A 2-[(3R)-3-methylmorpholin-4-yl]-4-(1-methyl-1H-pyrazol-5-yl)-8-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-1,7-naphthyridine (78.4 g, 171 mmol) was dissolved in 340 mL methanol. 340 mL conc, aqueous HCl solution (37 %) was added dropwise at room temperature and the reaction mixture was stirred 1 h at this temperature. After complete conversion (TLC control) 1500 mL 3M aqueous NaOH solution were added dropwise under cooling. The suspension was extracted twice with each 2000 mL dichloromethane. The combined organic phases were washed once with 2000 mL brine, dried over MgSC and the solvent was evaporated in vacuo. The residue was suspended in 150 mL acetonitrile and the suspension was filtered. The filter cake was washed with n-hexane and dried in vacuo at 50 °C yielding the title compound as a yellow solid (34.5 g, 91.9 mmol, 51 % yield).
280 mg With sulfuric acid at 20℃; for 3h;
  • 8
  • [ 2488945-27-1 ]
  • [ 1876467-74-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: lithium hexamethyldisilazane / N,N-dimethyl-formamide; tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere 2: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 16 h / 90 °C / Inert atmosphere; Microwave irradiation 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C / Inert atmosphere 4: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / water; 1,2-dimethoxyethane / 0.33 h / 130 °C / Microwave irradiation 5: sulfuric acid / 3 h / 20 °C
  • 10
  • [ 2411910-79-5 ]
  • [ 1876467-74-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; ethyl acetate / 1 h / 65 °C 2: hydrogenchloride; water / dichloromethane; methanol / 0.17 h / 0 - 22 °C / Large scale
  • 11
  • [ 2411910-78-4 ]
  • [ 1876467-74-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium hydrogencarbonate / Isopropyl acetate; water / 2.5 h / 50 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; ethyl acetate / 1 h / 65 °C 3: hydrogenchloride; water / dichloromethane; methanol / 0.17 h / 0 - 22 °C / Large scale
Same Skeleton Products
Historical Records