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[ CAS No. 1268454-23-4 ] {[proInfo.proName]}

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Chemical Structure| 1268454-23-4
Chemical Structure| 1268454-23-4
Structure of 1268454-23-4 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1268454-23-4 ]

CAS No. :1268454-23-4 MDL No. :MFCD15146372
Formula : C19H17N5O3 Boiling Point : -
Linear Structure Formula :- InChI Key :BLGWHBSBBJNKJO-UHFFFAOYSA-N
M.W : 363.37 Pubchem ID :70798655
Synonyms :
MLN1117;INK1117;TAK-117
Chemical Name :(6-(2-Aminobenzo[d]oxazol-5-yl)imidazo[1,2-a]pyridin-3-yl)(morpholino)methanone

Calculated chemistry of [ 1268454-23-4 ]

Physicochemical Properties

Num. heavy atoms : 27
Num. arom. heavy atoms : 18
Fraction Csp3 : 0.21
Num. rotatable bonds : 3
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 103.0
TPSA : 98.89 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.88 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.52
Log Po/w (XLOGP3) : 2.3
Log Po/w (WLOGP) : 1.82
Log Po/w (MLOGP) : 0.86
Log Po/w (SILICOS-IT) : 1.33
Consensus Log Po/w : 1.77

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.84
Solubility : 0.0529 mg/ml ; 0.000145 mol/l
Class : Soluble
Log S (Ali) : -4.01
Solubility : 0.0351 mg/ml ; 0.0000967 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -4.85
Solubility : 0.00517 mg/ml ; 0.0000142 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.11

Safety of [ 1268454-23-4 ]

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 [ 1268454-23-4 ]

* 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.

  • Upstream synthesis route of [ 1268454-23-4 ]
  • Downstream synthetic route of [ 1268454-23-4 ]

[ 1268454-23-4 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 1404480-15-4 ]
  • [ 1434089-03-8 ]
  • [ 1268454-23-4 ]
YieldReaction ConditionsOperation in experiment
85%
Stage #1: at 20℃; for 0.166667 h;
Stage #2: With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 20 - 102℃; Inert atmosphere; Reflux
[00342] Example6[00343] Formula I[00344] Preparation of (6-(2-aminobenzo [d] oxazol-5 -yl)imidazo [ 1 ,2-a]pyridin-3 - yl)(morpholino)methanone (Formula I):[00345] 1. A 5 L three-neck round bottom flask was equipped with a mechanical stirrer, thermocouple probe, Nitrogen / vacuum inlet and reflux condenser and placed into a heating mantle.[00346] 2. 1,4-Dioxane (3.75 L) and water (1.25 L) were added at room temperature.[00347] 3. Compound 9 (250 g) and Compound 3 (210 g) were added to the flask at room temperature.[00348] 4. The reaction mixture was stirred for 10 min at room temperature.[00349] 5. Sodium carbonate (300 g) was added to the flask followed byPd(PPh3)4 (47 g) undemitrogen at room temperature.[00350] 6. With stirring, the reactor was sparged with nitrogen for -30 minutes at [00351] 7. The reaction mixture was deoxygenated by performing 5 to 6 vacuum / nitrogen cycles.[00352] 8. The reaction mixture was heated to reflux (88°C to 102°C) under slight nitrogen bubbling and stirredfor 5 to 8 hours.[00353] 9. The reaction was monitored by HPLC.[00354] 10. Upon completion, the reaction mixture was cooled to 75 - 80°C.[00355] 11. Water (3.75 L) and ethyl acetate (1.25 L) were added to the reaction mixture at 75 - 80°C.[00356] 12. The resulting mixture was cooled to room temperature and stirred for 2 hours at room temperature.[00357] 13. The mixture was filtered and the solid collected was washed with water (2x 1.25 L), methanol (1.25 L) andethyl acetate (2 x 1.25 L).[00358] 14. The solidwas suspended in ethyl acetate (1.5 L) at room temperature for 1 hour.[00359] 15. The suspension was filtered and the solidcollected was washed with ethyl acetate (250 mL).[00360] 16. This process was repeated two more times.[00361] 17. The solidobtained was dried under vacuum to give a crude product (250 g, 85percent yield; HPLC purity 98.1percent; Pd level 1831 ppm).[00362] Further purification of the crude product:[00363] 18. The crude product (250g) was suspended in methanol (2.5 L) and HCl (158 mL) at room temperature.[00364] 19. The mixture was heated to 40 to 45°C to give a slightly cloudy solution.[00365] 20. Charcoal (250 g) was added to the reaction mixture at 40 to 45°C. [00366] 21. The resulting mixture was stirred for 30 minutes at 40 to 45 °C.[00367] 22. The hot solution was filtered through a poly pad with 2 inch celite bed and the cake was washed withmethanol (3 x 500 mL).[00368] 23. The solution was recharged to the flask (Pd level: 330 ppm).[00369] 24. The solution was heated to 40 to 45°C.[00370] 25. Charcoal (50 g) and silica thiol (50 g) were added at 40 to 45°C.[00371] 26. The mixture was stirred for 30 minutes at 40 to 45°C.[00372] 27. The hot solution was filtered through a poly pad and the cake was washed with methanol (250 mL)[00373] 28. This process was repeated one more time.[00374] 29. The methanol was removed under vacuum at 30 - 35°C to ~2.5 L.[00375] 30. The solution was cooled to 10 to 15°C.[00376] 31. Concentrated aqueous ammonia solution (200 mL) was added until reaching pH 8-9.[00377] 32. The reaction mixture was cooled to 0 to 5°C and stirred for 1 to 2 hours at 0 to 5°C.[00378] 33. The mixture was filtered and the cake was washed with water (2 x 500 mL) and methanol (2 x 500mL).[00379] 34. The solid collected was transfered back into a round bottom flask and suspended in ethyl acetate (2.5 L) at roomtemperature for 2 to 3 hours.[00380] 35. The solid was collected by filtration and washed with ethyl acetate (750 mL).36. The solid was dried under vacuum at ~50°C to constant weight to give thecompound of Formila I as an off-white solid (180 g, 61percent yield; HPLC purity 98.5percent; 'HNMR (DMSO-d6, 300 MHz) ? 9.1 (s, 1H), 8.1 (s, 1H), 7.8-7.65 (2H), 7.60-7.40 (m, 4H), 7.3-7.2 (1H), 3.8-3.6 (m, 8H); Pd level lppm).
61% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 20 - 102℃; Inert atmosphere Example 6 Preparation of (6-(2-aminobenzo [d] oxazol-5 -yl)imidazo [1,2-a]pyridin-3 -yl)(morpholino)methanone (Formula V): 1. A 5 L three-neck round bottom flask was equipped with a mechanical stirrer, thermocouple probe, Nitrogen / vacuum inlet and reflux condenser and placed into a heating mantle. 2. 1,4-Dioxane (3.75 L) and water (1.25 L) were added at room temperature. 3. Compound 9 (250 g) and Compound 3 (210 g) were added to the flask at room temperature. 4. The reaction mixture was stirred for 10 min at room temperature. 5. Sodium carbonate (300 g) was added to the flask followed byPd(PPh3)4 (47 g) undemitrogen at room temperature. 6. With stirring, the reactor was sparged with nitrogen for -30 minutes at < 20°C. 7. The reaction mixture was deoxygenated by performing 5 to 6 vacuum / nitrogen cycles. 8. The reaction mixture was heated to reflux (88°C to 102°C) under slight nitrogen bubbling and stirredfor 5 to 8 hours. 9. The reaction was monitored by HPLC. 10. Upon completion, the reaction mixture was cooled to 75 - 80°C. 11. Water (3.75 L) and ethyl acetate (1.25 L) were added to the reaction mixture at 75 - 80°C. 12. The resulting mixture was cooled to room temperature and stirred for 2 hours at room temperature. 13. The mixture was filtered and the solid collected was washed with water (2x 1.25 L), methanol (1.25 L) andethyl acetate (2 x 1.25 L). 14. The solidwas suspended in ethyl acetate (1.5 L) at room temperature for 1 hour. 15. The suspension was filtered and the solidcollected was washed with ethyl acetate (250 mL). 16. This process was repeated two more times. 17. The solidobtained was dried under vacuum to give a crude product (250 g, 85percent yield; HPLC purity 98.1percent; Pd level 1831 ppm). Further purification of the crude product: 18. The crude product (250g) was suspended in methanol (2.5 L) and HCl (158 mL) at room temperature. 19. The mixture was heated to 40 to 45°C to give a slightly cloudy solution. 20. Charcoal (250 g) was added to the reaction mixture at 40 to 45°C. 21. The resulting mixture was stirred for 30 minutes at 40 to 45 °C. 22. The hot solution was filtered through a poly pad with 2 inch celite bed and the cake was washed with methanol (3 x 500 mL). 23. The solution was recharged to the flask (Pd level: 330 ppm). 24. The solution was heated to 40 to 45°C. 25. Charcoal (50 g) and silica thiol (50 g) were added at 40 to 45°C. 26. The mixture was stirred for 30 minutes at 40 to 45°C. 27. The hot solution was filtered through a poly pad and the cake was washed with methanol (250 mL). 28. This process was repeated one more time. 29. The methanol was removed under vacuum at 30 - 35°C to ∼2.5 L. 30. The solution was cooled to 10 to 15°C. 31. Concentrated aqueous ammonia solution (200 mL) was added until reaching pH 8-9. 32. The reaction mixture was cooled to 0 to 5°C and stirred for 1 to 2 hours at 0 to 5°C. 33. The mixture was filtered and the cake was washed with water (2 x 500 mL) and methanol (2 x 500mL). 34. The solid collected was transfered back into a round bottom flask and suspended in ethyl acetate (2.5 L) at roomtemperature for 2 to 3 hours. 35. The solid was collected by filtration and washed with ethyl acetate (750 mL). 36. The solid was dried under vacuum at ∼50°C to constant weight to give thecompound of Formila I as an off-white solid (180 g, 61percent yield; HPLC purity 98.5percent; 'HNMR (DMSO-d6, 300 MHz) δ 9.1 (s, 1H), 8.1 (s, 1H), 7.8-7.65 (2H), 7.60-7.40 (m, 4H), 7.3-7.2 (1H), 3.8-3.6 (m, 8H); Pd level lppm).
Reference: [1] Patent: WO2013/71272, 2013, A1, . Location in patent: Paragraph 00342-00380
[2] Patent: EP2792360, 2014, A1, . Location in patent: Paragraph 0226-0227
  • 2
  • [ 944896-42-8 ]
  • [ 1268454-23-4 ]
Reference: [1] Patent: WO2013/71272, 2013, A1,
[2] Patent: EP2792360, 2014, A1,
  • 3
  • [ 40925-68-6 ]
  • [ 1268454-23-4 ]
Reference: [1] Patent: WO2013/71272, 2013, A1,
[2] Patent: EP2792360, 2014, A1,
  • 4
  • [ 64037-07-6 ]
  • [ 1268454-23-4 ]
Reference: [1] Patent: WO2013/71272, 2013, A1,
[2] Patent: EP2792360, 2014, A1,
  • 5
  • [ 372198-69-1 ]
  • [ 1268454-23-4 ]
Reference: [1] Patent: WO2013/71272, 2013, A1,
  • 6
  • [ 1224844-66-9 ]
  • [ 1268454-23-4 ]
Reference: [1] Patent: WO2013/71272, 2013, A1,
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