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[ CAS No. 1627856-64-7 ] {[proInfo.proName]}

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Chemical Structure| 1627856-64-7
Chemical Structure| 1627856-64-7
Structure of 1627856-64-7 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1627856-64-7 ]

CAS No. :1627856-64-7 MDL No. :MFCD30747847
Formula : C22H21F4N3O4 Boiling Point : -
Linear Structure Formula :- InChI Key :IDXKJSSOUXWLDB-UHFFFAOYSA-N
M.W : 467.41 Pubchem ID :78427026
Synonyms :
RET KInase inhibitor 1;​RET Kinase Inhibitor 1

Calculated chemistry of [ 1627856-64-7 ]

Physicochemical Properties

Num. heavy atoms : 33
Num. arom. heavy atoms : 17
Fraction Csp3 : 0.32
Num. rotatable bonds : 9
Num. H-bond acceptors : 9.0
Num. H-bond donors : 2.0
Molar Refractivity : 112.08
TPSA : 97.22 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.75 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.36
Log Po/w (XLOGP3) : 3.38
Log Po/w (WLOGP) : 6.08
Log Po/w (MLOGP) : 3.06
Log Po/w (SILICOS-IT) : 5.79
Consensus Log Po/w : 4.33

Druglikeness

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

Water Solubility

Log S (ESOL) : -4.65
Solubility : 0.0104 mg/ml ; 0.0000222 mol/l
Class : Moderately soluble
Log S (Ali) : -5.1
Solubility : 0.00371 mg/ml ; 0.00000794 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -8.59
Solubility : 0.0000012 mg/ml ; 0.0000000026 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 3.65

Safety of [ 1627856-64-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1627856-64-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1627856-64-7 ]

[ 1627856-64-7 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 1627857-70-8 ]
  • [ 1627856-64-7 ]
YieldReaction ConditionsOperation in experiment
77% With trifluoroacetic acid In dichloromethane at 25℃; for 2h; 30.4 2-(4-(4-Ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide To a suspension of 2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(5- (l, l, l-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide (100 g, 170 mmol) in DCM (1 L) was added TFA (80 mL, 1077 mmol) dropwise. The mixture was stirred at 25 °C for 2 h. The mixture was then concentrated. To the residue was added H20 (500 mL) dropwise and then neutralized with saturated Na2CC>3 solution to adjust pH = 7.5. The precipitate was filtered, washed with H20 (350 mL x 3) and dried in vacuo. To the solid was added PE/EA (3: 1, v/v, 300 mL) and stirred for 0.5 h. The solid was filtered and washed with PE/EA (3: 1, v/v, 100 mL x 2). The solid was redissolved in DCM/MeOH (20: 1, v/v, 1.5 L) and then concentrated in vacuo to a minimal amount of solvent (about 150 mL). The solid was filtered, washed with CH3CN (50 mL x 2) and dried in vacuo. The residual solid was added to EtOH (2.5 L) and heated to 80 °C. After the solid was dissolved completely, the mixture was concentrated in vacuo to give a white solid of 2-(4-(4-ethoxy-6-oxo- 1 ,6-dihydropyridin-3 -yl)-2-fluorophenyl)-N-(5 -( 1,1, 1 -trifluoro-2- methylpropan-2-yl)isoxazol-3-yl)acetamide (61.4 g, 131 mmol, 77% yield): l NMR (400 MHz, CD3OD) δ 7.40-7.30 (m, 2H), 7.25-7.18 (m, 2H), 6.88 (s, 1H), 5.98 (s, 1H), 4.11 (q, J = 7.2 Hz, 2H), 3.81 (s, 2H), 1.56 (s, 6H), 1.37 (t, J= 7.2 Hz, 3H); ES-LCMS m/z: 468 (M+H).
77% With trifluoroacetic acid In dichloromethane at 25℃; for 2h; 1.13 Preparation of:2-(4-(4-Ethoxy-6-oxo- 1 ,6-dihydropyridin-3 -yl)-2-fluorophenyl)-N-(5-(1, 1,1 -trifluoro-2-methylpropan-2-yl)i soxazol-3 -yl)acetamide (Compound A)Step 13: 2-(4-(4-Ethoxy-6-oxo- 1, 6-dihydropyridin-3 -yl)-2-fluorophenyl)-N-(5 - (1,1,1 -trifluoro-2-methylpropan-2-yl)i soxazol-3 -yl)acetamide To a suspension of 2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3 -yl)-2-fluorophenyl)-N-(5 -(1,1,1 -trifluoro-2-methylpropan-2-yl)i soxazol-3 -yl)acetamide (100 g,170 mmol) in DCM (1 L) was added TFA (80 mL, 1077 mmol) dropwise. The mixturewas stirred at 25 °C for 2 h. The mixture was then concentrated. To the residue was addedH20 (500 mL) dropwise and then neutralized with saturated Na2CO3 solution to adjust pH= 7.5. The precipitate was filtered, washed with H20 (350 mL x 3) and dried in vacuo. Tothe solid was added PE/EA (3:1, v/v, 300 mL) and stirred for 0.5 h. The solid was filteredand washed with PE/EA (3:1, v/v, 100 mL x 2). The solid was redissolved in DCM/MeOH (20:1, v/v, 1.5 L) and then concentrated in vacuo to a minimal amount of solvent (about 150 mL). The solid was filtered, washed with MeCN (50 mL x 2) and dried in vacuo. The residual solid was added to EtOH (2.5 L) and heated to 80 °C. After the solid wasdissolved completely, the mixture was concentrated in vacuo to give a white solid of 2-(4- (4-ethoxy-6-oxo- 1, 6-dihydropyridin-3 -yl)-2-fluorophenyl)-N-(5 -(1,1,1 -trifluoro-2- methylpropan-2-yl)isoxazol-3-yl)acetamide (61.4 g, 131 mmol, 77%): ‘H NMR (400 MFIz, CD3OD) ö 7.40-7.30 (m, 2H), 7.25-7.18 (m, 2H), 6.88 (s, 1H), 5.98 (s, 1H), 4.11 (q, J= 7.2 Hz, 2H), 3.81 (s, 2H), 1.56 (s, 6H), 1.37 (t, J= 7.2 Hz, 3H); ES-LCMS m/z: 468 (M+H).
77% With trifluoroacetic acid In dichloromethane at 25℃; for 2h;
  • 2
  • [ 114897-91-5 ]
  • 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(5-(1,1,1- trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide [ No CAS ]
  • 3
  • [ 76283-09-5 ]
  • [ 1627856-64-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1: ethanol / 12 h / 60 °C / Inert atmosphere 2: sodium hydroxide; methanol / 12 h / 100 °C 3: sulfuric acid / Reflux 4: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 4 h / Inert atmosphere; Reflux 5: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 6: lithium hydroxide monohydrate; water / tetrahydrofuran / 10 h / 60 °C 7: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 8: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 8 steps 1: ethanol / 12 h / 60 °C / Inert atmosphere 2: sodium hydroxide; methanol / 20 - 80 °C / Inert atmosphere 3: sulfuric acid / Reflux 4: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 4 h / Reflux; Inert atmosphere 5: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / water; 1,4-dioxane / 2 h / Inert atmosphere; Reflux 6: lithium hydroxide monohydrate; water / 60 °C 7: pyridine; propylphosphonic anhydride / 1 h / 25 °C 8: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 8 steps 1: ethanol / 12 h / 60 °C / Inert atmosphere 2: sodium hydroxide; methanol / 5 h / 80 °C / Inert atmosphere 3: sulfuric acid / water / Reflux 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 4 h / Inert atmosphere; Reflux 5: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 6: water; lithium hydroxide monohydrate / tetrahydrofuran / 10 h / 60 °C 7: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 8: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
  • 4
  • [ 114897-92-6 ]
  • 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(5-(1,1,1- trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide [ No CAS ]
  • 5
  • [ 1188911-73-0 ]
  • [ 1627856-64-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: hydroxylamine hydrochloride; sodium hydrogencarbonate / methanol; water / 15 h / 0 - 65 °C / pH 7.5 1.2: 2 h / pH 1 / Reflux 2.1: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 3.1: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 3 steps 1: hydroxylamine hydrochloride; sodium hydrogencarbonate / water; methanol / 15 h / 0 - 65 °C / pH 7.5 2: pyridine; propylphosphonic anhydride / 1 h / 25 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 3 steps 1: hydroxylamine hydrochloride; sodium hydrogencarbonate / water; methanol / 15 h / 65 °C / pH 7.5 2: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
  • 6
  • [ 1188911-72-9 ]
  • 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(5-(1,1,1- trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide [ No CAS ]
  • 7
  • [ 1188911-74-1 ]
  • [ 1627857-10-6 ]
  • [ 1627856-64-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 2 steps 1: pyridine; propylphosphonic anhydride / 1 h / 25 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 2 steps 1: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
  • 8
  • [ 52311-50-9 ]
  • 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(5-(1,1,1- trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide [ No CAS ]
  • 9
  • [ 23056-36-2 ]
  • [ 1627856-64-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1: tetrahydrofuran / 10 h / 25 °C 2: sulfuric acid; N-Bromosuccinimide / 10 h / 60 °C 3: potassium hydroxide; 18-crown-6 ether / toluene / 2 h / 120 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 5: lithium hydroxide monohydrate; water / tetrahydrofuran / 10 h / 60 °C 6: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 7: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 7 steps 1: tetrahydrofuran / 12 h / 0 - 25 °C / Large scale 2: sulfuric acid; N-Bromosuccinimide / 3 h / 80 °C 3: potassium hydroxide; 18-crown-6 ether / toluene / 2 h / 120 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / water; 1,4-dioxane / 2 h / Inert atmosphere; Reflux 5: lithium hydroxide monohydrate; water / 60 °C 6: pyridine; propylphosphonic anhydride / 1 h / 25 °C 7: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 7 steps 1: tetrahydrofuran / 12 h / 0 - 25 °C 2: sulfuric acid; N-Bromosuccinimide / 3 h / 80 °C 3: 18-crown-6 ether; potassium hydroxide / toluene / 2 h / 120 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 5: water; lithium hydroxide monohydrate / tetrahydrofuran / 10 h / 60 °C 6: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 7: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
  • 10
  • [ 52311-48-5 ]
  • [ 1627856-64-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: potassium hydroxide; 18-crown-6 ether / toluene / 2 h / 120 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 3: lithium hydroxide monohydrate; water / tetrahydrofuran / 10 h / 60 °C 4: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 5: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 5 steps 1: potassium hydroxide; 18-crown-6 ether / toluene / 2 h / 120 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / water; 1,4-dioxane / 2 h / Inert atmosphere; Reflux 3: lithium hydroxide monohydrate; water / 60 °C 4: pyridine; propylphosphonic anhydride / 1 h / 25 °C 5: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 5 steps 1: 18-crown-6 ether; potassium hydroxide / toluene / 2 h / 120 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 3: water; lithium hydroxide monohydrate / tetrahydrofuran / 10 h / 60 °C 4: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 5: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
  • 11
  • [ 1627857-11-7 ]
  • [ 1627856-64-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 2: lithium hydroxide monohydrate; water / tetrahydrofuran / 10 h / 60 °C 3: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / water; 1,4-dioxane / 2 h / Inert atmosphere; Reflux 2: lithium hydroxide monohydrate; water / 60 °C 3: pyridine; propylphosphonic anhydride / 1 h / 25 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 2: water; lithium hydroxide monohydrate / tetrahydrofuran / 10 h / 60 °C 3: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
  • 12
  • [ 193290-19-6 ]
  • 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(5-(1,1,1- trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide [ No CAS ]
  • 13
  • [ 1415960-53-0 ]
  • [ 1627856-64-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 2: lithium hydroxide monohydrate; water / tetrahydrofuran / 10 h / 60 °C 3: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / water; 1,4-dioxane / 2 h / Inert atmosphere; Reflux 2: lithium hydroxide monohydrate; water / 60 °C 3: pyridine; propylphosphonic anhydride / 1 h / 25 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 2: water; lithium hydroxide monohydrate / tetrahydrofuran / 10 h / 60 °C 3: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
  • 14
  • [ 1627857-12-8 ]
  • [ 1627856-64-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: lithium hydroxide monohydrate; water / tetrahydrofuran / 10 h / 60 °C 2: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 3 steps 1: lithium hydroxide monohydrate; water / 60 °C 2: pyridine; propylphosphonic anhydride / 1 h / 25 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
Multi-step reaction with 3 steps 1: water; lithium hydroxide monohydrate / tetrahydrofuran / 10 h / 60 °C 2: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / 1 h / 25 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
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