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Chemical Structure| 545445-40-7
Chemical Structure| 545445-40-7
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Product Details of [ 545445-40-7 ]

CAS No. :545445-40-7 MDL No. :MFCD18072442
Formula : C9H14N2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :SRICXDSOENVWEU-UHFFFAOYSA-N
M.W : 182.22 Pubchem ID :21891460
Synonyms :

Calculated chemistry of [ 545445-40-7 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.67
Num. rotatable bonds : 1
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 55.49
TPSA : 41.57 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.37 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.75
Log Po/w (XLOGP3) : 0.06
Log Po/w (WLOGP) : -1.04
Log Po/w (MLOGP) : -0.36
Log Po/w (SILICOS-IT) : 0.84
Consensus Log Po/w : 0.25

Druglikeness

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

Water Solubility

Log S (ESOL) : -0.94
Solubility : 20.8 mg/ml ; 0.114 mol/l
Class : Very soluble
Log S (Ali) : -0.49
Solubility : 59.5 mg/ml ; 0.326 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.15
Solubility : 13.0 mg/ml ; 0.0716 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.91

Safety of [ 545445-40-7 ]

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 [ 545445-40-7 ]

* 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.

  • Upstream synthesis route of [ 545445-40-7 ]
  • Downstream synthetic route of [ 545445-40-7 ]

[ 545445-40-7 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 545445-40-7 ]
  • [ 27143-07-3 ]
  • [ 503614-56-0 ]
YieldReaction ConditionsOperation in experiment
81.2% With N-ethyl-N,N-diisopropylamine In ethyl acetate at 85 - 95℃; for 20 h; Inert atmosphere; Green chemistry Under nitrogen atmosphere, ethyl acetate (360 mL) was added with 18.2 g of 5,6-dihydro-3-(4-morpholinyl)-2(1H)-pyridone andEthyl [(4-methoxyphenyl)hydrazino]chloroacetate 30.8 g, 19.4 g of diisopropylethylamine was added under stirring, and the reaction was heated to 85 to 95°C and stirred for 20 hours. After cooling to 15 to 25° C., 35 mL of trifluoroacetic acid was added dropwise after filtration, followed by stirring at 15 to 25° C. for 2 hours.Adding 10percent sodium bicarbonate solution to quench the mass percentage (the mass percentage refers to the percentage of sodium bicarbonate in the total mass of aqueous sodium bicarbonate, the same below), and then extracted with ethyl acetate 1 Times.The organic phase was washed with a 10percent by weight aqueous solution of sodium bicarbonate and a 15percent by weight saline solution (the mass percent containedThe amount refers to the percentage of sodium chloride in the total mass of the saline solution) and is dried over anhydrous sodium sulfate.Filtration and concentration in vacuo (45-55°C, -0.085 MPa--0.1 MPa) afforded a yellow solid.The yellow solid was added to 150 mL of ethyl acetate, heated to 75-85°C and stirred for 1 hour to dissolve, cooled to 0-5°C and stirred for 2 hours, filtered, washed with 0-5°C ethyl acetate, and dried at -0.01. Vacuum drying at MPa--0.1MPa, 45-55°C for 8 hours to 12 hours to obtain a pale yellow solid25.6 g, yield 81.2percent, HPLC purity 98.30percent.
Reference: [1] Patent: CN107955002, 2018, A, . Location in patent: Paragraph 0082-0097
[2] Patent: CN105384739, 2016, A, . Location in patent: Paragraph 0205; 0208; 0209; 0214
  • 2
  • [ 545445-40-7 ]
  • [ 503614-56-0 ]
Reference: [1] Patent: WO2004/83177, 2004, A2, . Location in patent: Page 176-177
  • 3
  • [ 545445-40-7 ]
  • [ 503614-56-0 ]
Reference: [1] Patent: CN104327074, 2016, B,
[2] Patent: CN104311558, 2016, B,
[3] Patent: CN104277041, 2016, B,
[4] Patent: CN104311574, 2016, B,
[5] Patent: CN104311575, 2016, B,
[6] Patent: CN104277039, 2016, B,
[7] Patent: CN104311557, 2016, B,
[8] Patent: CN104277040, 2016, B,
[9] Patent: CN104277038, 2016, B,
[10] Patent: EP3147283, 2017, A1,
[11] Patent: CN104513239, 2017, B,
  • 4
  • [ 110-91-8 ]
  • [ 41419-12-9 ]
  • [ 545445-40-7 ]
YieldReaction ConditionsOperation in experiment
92% With triethylamine In 1,4-dioxane at 110℃; for 4.5 h; At room temperature 100 g (0.60 µM) intermediate (2) dissolved in 400 ml 1, 4 - dioxane, adding 60 ml (0.66 µM) morpholine and 210 ml (1.50 µM) triethylamine. Raising the temperature to 110 °C. TLC detection 4.5 h reaction finishes, cooling to room temperature, still precipitate solid. Filtered, and the filtrate is distilled under reduced pressure to, the evaporation to get the yellow solid, washing with ethyl ether (2 × 400 ml), washed with water (2 × 200 ml), dried to obtain the white solid powder 100.5 g (theoretical yield is 108.5 g), yield is 92percent.
74% for 2 h; Reflux Morpholine (14 cm3) and 7 g 10 (0.0417 mol) werecharged into a 50 cm3 single neck round-bottomed flask,equipped with a stir bar, a condenser, and a CaCl2 guardtube. The resulting mixture was refluxed for 2 h, cooled toRT, and poured into 50 cm3 ice cold water. The product was extracted with dichloromethane (3 9 40 cm3). Theorganic layers were combined, washed with 30 cm3 water and 30 cm3 brine, dried over Na2SO4, and concentrated under reduced pressure at<45 °C. The crude material thus obtained was stirred with 15 cm3 MTBE at RT for 10 min,filtered, washed with 10 cm3 n-hexane, and dried at RT for 4 h to obtain 12 (5.6 g, 74percent, 95.3percent purity by HPLC analysis) as a dark brown solid. 1H NMR spectral data of 12 (see Supplementary Material for details) was inagreement with that reported in Ref. [14].
55% at 140℃; for 12 h; The 3,3-dichloro-piperidine-2-one (22.0g, 131 . 7mmol) dissolved in morpholine (80 ml) in. Then heating to 140 °C stirring 12 hours. Cooling to room temperature, solvent evaporate under reduced pressure. The crude product after column chromatography purification (dichloromethane/methanol (v/v)=20/1), get white solid (13g, 55percent).
55% at 140℃; for 12 h; 3,3-dichloropiperidin-2-one (22.0g, 131.7mmol) It was dissolved in morpholine (80mL) then stirred and heated to 140°C for 12 hours. Cooled to room temperature, the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (v / v) = 20/1) giving a white solid (13g, 55percent).
55% at 140℃; for 12 h; The 3, 3- [...] -2-one (22.0g, 131 . 7mmol) dissolved in morpholine (80 ml) in. Then heating to 140 °C stirring 12 hours. Cooling to room temperature, solvent evaporate under reduced pressure. The crude product after column chromatography purification (dichloromethane/methanol (v/v)=20/1), get white solid (13g, 55percent).
55% at 140℃; for 12 h; The 3,3-dichloropiperidine 2-one(22.0g, 131.7mmol) was dissolved in morpholine (80mL) in.Then heated to 140 stirred for 12 hours.Cooled to room temperature, the solvent was distilled off under reduced pressure.The crude product was purified by column chromatography (dichloromethane / methanol (v / v) = 20/1), as a white solid (13g, 55percent).
55% at 140℃; for 12 h; The 3,3-dichloro-2-one (22.0g, 131.7mmol) was dissolved in morpholine (80mL) in. Then heated to 140 stirred for 12 hours. Cooled to room temperature, the solvent was distilled off under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (v / v) = 20/1), as a white solid (13g, 55percent).
55% at 140℃; for 12 h; A solution of 3,3-dichloropiperidin-2-one (22.Og, 131.7 mmol)Dissolved in morpholine(80 mL).Then heated toThe mixture was stirred at 140 ° C for 12 hours. Cool to room temperature and evaporate the solvent under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (v /Ν) = 20/1) to give a white solid (13 g, 55percent).
55% at 140℃; for 12 h; 3, 3-dichloropiperidin-2-one (22. 0 g, 131.7 mmol) was dissolved in morpholine (80 mL).And then heated to 140 ° C for 12 hours.Cool to room temperature and evaporate the solvent under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (v / v = 20/1) to give a white solid (13 g, 55percent).
55% at 140℃; for 12 h; 3-Morpholine-5,6-dihydropyridine-2 (1 H) -one[0145] 3,3-Dichloropiperidin-2-one (22. 0 g, 131.7 mmol) was dissolved in morpholine (80 mL). And then heated to 140 ° C for 12 hours. Cool to room temperature and evaporate the solvent under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (v / v = 20/1) to give a white solid (13 g, 55percent).
55% at 140℃; for 12 h; 3,3-dichloropiperidin-2-one (22.0 g, 131.7 mmol) was dissolved in morpholine (80 mL).Followed by heating to 140 ° C for 12 hours.Cool to room temperature and evaporate the solvent under reduced pressure.The crude product was purified by column chromatography (dichloromethane / methanol (v / v) = 20/1) to give a white solid (13 g, 55percent).
23 g at 130℃; Step B:
3,3-Dichloropiperidin-2-one (31 g, crude) was dissolved in morpholine (300 mL), the mixture was heated to 130 °C overnight.
The solvent was removed by concentration, and then washed with dichloromethane.
The solid was filtered, the organic layer was concentrated, and the crude was purified by chromatography to give 3-morpholino-5,6-dihydropyridin-2(1H)-one (23 g).
1H NMR (CDCl3, 400 MHz): δ = 6.58-6.50(m, 1H), 5.55(t, J = 4.8 Hz, 1H), 3.85-3.79(m, 4H), 3.32(td, J = 6.8, 3.2 Hz, 2H), 2.87(t, J = 4.8 Hz, 4 H), 2.35(td, J =6.8, 4.8 Hz, 2H).

Reference: [1] Patent: CN104513239, 2017, B, . Location in patent: Paragraph 0197; 0238; 0241; 0242
[2] Monatshefte fur Chemie, 2017, vol. 148, # 8, p. 1477 - 1482
[3] Patent: CN104327074, 2016, B, . Location in patent: Paragraph 0151; 0152; 0153
[4] Patent: CN104311558, 2016, B, . Location in patent: Paragraph 0150; 0151; 0152
[5] Patent: CN104277041, 2016, B, . Location in patent: Paragraph 0155; 0156; 0157
[6] Patent: CN104311574, 2016, B, . Location in patent: Paragraph 0147; 0148
[7] Patent: CN104277039, 2016, B, . Location in patent: Paragraph 0151; 0152; 0153
[8] Patent: CN104311557, 2016, B, . Location in patent: Paragraph 0140-0141
[9] Patent: CN104311575, 2016, B, . Location in patent: Paragraph 0154; 0155
[10] Patent: CN104277040, 2016, B, . Location in patent: Paragraph 0144-0146
[11] Patent: CN104277038, 2016, B, . Location in patent: Paragraph 0153-0155
[12] Patent: WO2004/83177, 2004, A2, . Location in patent: Page 161
[13] Patent: EP3147283, 2017, A1, . Location in patent: Paragraph 0083
  • 5
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  • [ 207976-92-9 ]
  • [ 545445-40-7 ]
YieldReaction ConditionsOperation in experiment
30.2% With lithium carbonate In N,N-dimethyl-formamide at 130℃; for 3 h; A solution of 3 (1.3 g, 100.0 mmol) and morpholine in DMF (5 mL) was treated with Li2CO3 (1.5 g, 20.3 mmol) at room temperature. The resulting mixture was then heated at 130 °C for 3 h. Then the reaction mixture was cooled down to 25 °C and filtered. The filtrate was concentrated and the residue was purified by flash chromatography (Ethyl Acetate/Petroleum Ether = 1:2). The product was obtained as a brown solid 4 (0.6 g, 30.2percent). M.p. 123-126 °C, 1H NMR (CDCl3, 300 MHz)δ: 6.15 (s, 1H, NH), 5.56 (t, J = 1.5 Hz, 1H, =CH), 3.82-3.85 (m, 4H, 2 CH2), 3.30-3.36 (m, 2H, CH2), 2.87-2.90 (m, 4H, 2 CH2), 2.33-2.40 (m, 2H, CH2); MS (ESI): 183.1 [M + H]+.
30.2% With lithium carbonate In N,N-dimethyl-formamide at 130℃; for 3 h; 1.3 g of 3-chloro-5,6-dihydro-2(1H)-pyridone and 0.9 g of morpholine were dissolved in 5 mL of DMF, 1.5 grams of anhydrous lithium carbonate was added, heated to 130 degrees, and reacted for 3 hours.. The reaction mixture was filtered, distilled under reduced pressure to remove the solvent and the residue was purified by column chromatography to give 0.6 g of a white solid, yield 30.2percent.
Reference: [1] European Journal of Medicinal Chemistry, 2014, vol. 82, p. 545 - 551
[2] Patent: CN103601670, 2016, B, . Location in patent: Paragraph 0080-0082
[3] Patent: US2003/181466, 2003, A1,
  • 6
  • [ 675-20-7 ]
  • [ 545445-40-7 ]
Reference: [1] European Journal of Medicinal Chemistry, 2014, vol. 82, p. 545 - 551
[2] Patent: CN104327074, 2016, B,
[3] Patent: CN104311558, 2016, B,
[4] Patent: CN104277038, 2016, B,
[5] Patent: CN103601670, 2016, B,
[6] Patent: CN104277041, 2016, B,
[7] Patent: CN104311574, 2016, B,
[8] Patent: CN104277039, 2016, B,
[9] Patent: CN104311557, 2016, B,
[10] Patent: CN104311575, 2016, B,
[11] Patent: CN104277040, 2016, B,
[12] Patent: EP3147283, 2017, A1,
[13] Monatshefte fur Chemie, 2017, vol. 148, # 8, p. 1477 - 1482
  • 7
  • [ 41419-12-9 ]
  • [ 545445-40-7 ]
Reference: [1] European Journal of Medicinal Chemistry, 2014, vol. 82, p. 545 - 551
  • 8
  • [ 1192-28-5 ]
  • [ 545445-40-7 ]
Reference: [1] Patent: CN104513239, 2017, B,
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