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[ CAS No. 333954-86-2 ] {[proInfo.proName]}

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Chemical Structure| 333954-86-2
Chemical Structure| 333954-86-2
Structure of 333954-86-2 * Storage: {[proInfo.prStorage]}
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Product Details of [ 333954-86-2 ]

CAS No. :333954-86-2 MDL No. :MFCD14155813
Formula : C17H22N2O3 Boiling Point : -
Linear Structure Formula :- InChI Key :ODHVBWQNZTWKCV-UHFFFAOYSA-N
M.W : 302.37 Pubchem ID :23019443
Synonyms :

Calculated chemistry of [ 333954-86-2 ]

Physicochemical Properties

Num. heavy atoms : 22
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.53
Num. rotatable bonds : 5
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 87.32
TPSA : 62.56 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.98 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.42
Log Po/w (XLOGP3) : 3.05
Log Po/w (WLOGP) : 2.96
Log Po/w (MLOGP) : 1.78
Log Po/w (SILICOS-IT) : 2.35
Consensus Log Po/w : 2.71

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 : 0.0939 mg/ml ; 0.00031 mol/l
Class : Soluble
Log S (Ali) : -4.03
Solubility : 0.0282 mg/ml ; 0.0000933 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -3.6
Solubility : 0.0751 mg/ml ; 0.000248 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 2.49

Safety of [ 333954-86-2 ]

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

Application In Synthesis of [ 333954-86-2 ]

* 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 [ 333954-86-2 ]
  • Downstream synthetic route of [ 333954-86-2 ]

[ 333954-86-2 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 1194-02-1 ]
  • [ 333954-86-2 ]
YieldReaction ConditionsOperation in experiment
91%
Stage #1: With sodium hydride In N,N-dimethyl-formamide at 20℃; for 1 h;
Stage #2: at 60℃; for 0.5 h;
Step A: tert-Butyl-4-(4-cvanophenyloxy)- 1 -piperidinecarboxylate <n="102"/>To tert-butyl 4-hydroxy- 1 -piperidinecarboxylate (24.1 g, 100. 0 mmol) in dimethylformamide (250 mL) is added sodium hydride (60percent emulsion in mineral oil) (8.00 g, 200.0 mmol) and the mixture is stirred at rt for 1 h. 4-Fluorobenzonitrile (12.1 g, 100.0 mmol) is added, the mixture is heated to 60 0C for 30 minutes, diluted with ethyl acetate and the reaction is quenched by the addition of water. The organic phase is evaporated in vacuo and purified on silica gel to give the desired product (27.5 g, 91percent).
Reference: [1] Patent: WO2007/106705, 2007, A1, . Location in patent: Page/Page column 100-101
  • 2
  • [ 1194-02-1 ]
  • [ 109384-19-2 ]
  • [ 333954-86-2 ]
YieldReaction ConditionsOperation in experiment
52%
Stage #1: With sodium hydride In DMF (N,N-dimethyl-formamide) at 50℃; for 0.75 h;
Stage #2: at 50℃; for 2 h;
Example 9 4- (1-Benzyl-piperidin-4-yloxy)-benzamide Step 1 4- (4-Cyano-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester Add a solution of N-Boc-4-hydroxypiperidine (3.0 g, 14.9 mmol) in DMF (5 mL) to a suspension of sodium hydride (894 mg, 22.4 mmol) in DMF (17 mL). Stir the reaction mixture while heating at 50°C for 45 min. Then add a solution of 4-fluoro- benzonitrile (2.16 g, 17.9 mmol) in DMF (5 mL). Stir and heat at 50°C for 2h. Let cool to room temperature and quench with water (0.5 mL). Evaporate DMF. Redissolved the resulting residue in EtOAc/hexanes (2/1,20 mL) and wash with water (3x15 mL). Dry the organic layer over magnesium sulfate, filter and concentrate. Purify by chromatography (EtOAc/hexanes 20percent and EtOAc/hexanes 10percent) to yield the title compound (2.32 g, 52percent).
Reference: [1] Patent: WO2005/61442, 2005, A1, . Location in patent: Page/Page column 44
[2] Patent: WO2004/37800, 2004, A1, . Location in patent: Page 26
[3] Patent: WO2004/37788, 2004, A1, . Location in patent: Page 17
  • 3
  • [ 767-00-0 ]
  • [ 118811-07-7 ]
  • [ 333954-86-2 ]
YieldReaction ConditionsOperation in experiment
55.8% With potassium carbonate In N,N-dimethyl-formamide at 100℃; Step (i): Preparation of 4-(4-Cyano phenoxy) piperidine-l-carboxylic acid tert-butyl esterA solution of 4-hydroxy benzonitrile (15 g, 0.126 moles), potassium carbonate (28.89 g, 0.208 moles) and 4-(Toluene-4-sulfonyloxy) piperidine-l-carboxylic acid tert-butyl ester (57.62 g, 0.162 moles) in dimethylformamide (150 mL) was stirred at 100 °C while monitoring the progress of the reaction by thin layer chromatography. After completion of reaction, the reaction mass was quenched on to water (400 mL) and extracted with ethyl acetate (3 x 300 mL). The resulting ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to obtain the crude residue, which was further purified by flash chromatography using (ethyl acetate: hexane,l :9) to afford the title compound 21.25 g (Yield: 55.8 percent). - NMR (δ ppm): 1.47 (9H, s), 1.74 - 1.80 (2H, m), 1.91 - 1.96 (2H, m) 3.33 - 3.40 (2H, m), 3.66 - 3.72 (2H, m), 4.53 - 4.57 (1H, m), 6.94 - 6.96 (2H, d, J = 8.78 Hz), 7.57 - 7.59 (2H, d, J = 8.76 Hz);Mass (m/z): 303.4 (M+H)+.
55.8% With potassium carbonate In N,N-dimethyl-formamide at 100℃; Step (i):
Preparation of 4-(4-Cyano phenoxy)piperidine-1-carboxylic acid tert-butyl ester
A solution of 4-hydroxy benzonitrile (15 g, 0.126 moles), potassium carbonate (28.89 g, 0.208 moles) and 4-(Toluene-4-sulfonyloxy)piperidine-1-carboxylic acid tert-butyl ester (57.62 g, 0.162 moles) in dimethylformamide (150 mL) was stirred at 100° C. while monitoring the progress of the reaction by thin layer chromatography.
After completion of reaction, the reaction mass was quenched on to water (400 mL) and extracted with ethyl acetate (3*300 mL).
The resulting ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to obtain the crude residue, which was further purified by flash chromatography using (ethyl acetate:hexane, 1:9) to afford the title compound 21.25 g
(Yield: 55.8percent).
1H-NMR (δ ppm): 1.47 (9H, s), 1.74-1.80 (2H, m), 1.91-1.96 (2H, m) 3.33-3.40 (2H, m), 3.66-3.72 (2H, m), 4.53-4.57 (1H, m), 6.94-6.96 (2H, d, J=8.78 Hz), 7.57-7.59 (2H, d, J=8.76 Hz);
Mass (m/z): 303.4 (M+H)+.
Reference: [1] Patent: WO2012/114348, 2012, A1, . Location in patent: Page/Page column 11
[2] Patent: US2014/135304, 2014, A1, . Location in patent: Paragraph 0115-0117
  • 4
  • [ 767-00-0 ]
  • [ 109384-19-2 ]
  • [ 333954-86-2 ]
YieldReaction ConditionsOperation in experiment
67.6% With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 25℃; for 4 h; Tert-butyl-4-hydroxypiperidine-1-carboxylate (4.5 g, 22.4 mmol)4-hydroxybenzonitrile (2.7 g, 22.7 mmol)And triphenylphosphine(8.8 g, 33.5 mmol) was dissolved in tetrahydrofuran (80 mL)Cooled to 0 ° C,Diethyl azodicarboxylate (5.8 g, 33.3 mmol) was added.25 ° C for 4 hours,LC-MS detection reaction is completed,Concentrated, ethyl acetate (150 mL) and water (50 mL) were added,The aqueous phase was extracted with ethyl acetate (50 mL)Combined organic phase,The residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) to give the product (4.6 g, 67.6percent yield).
Reference: [1] Patent: CN107226807, 2017, A, . Location in patent: Paragraph 0264-0266
  • 5
  • [ 1194-02-1 ]
  • [ 333954-86-2 ]
Reference: [1] Patent: WO2015/69110, 2015, A1, . Location in patent: Page/Page column 54; 55
  • 6
  • [ 623-03-0 ]
  • [ 109384-19-2 ]
  • [ 333954-86-2 ]
Reference: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 6, p. 2229 - 2238
  • 7
  • [ 79099-07-3 ]
  • [ 333954-86-2 ]
Reference: [1] Patent: CN107226807, 2017, A,
  • 8
  • [ 333954-86-2 ]
  • [ 609781-33-1 ]
Reference: [1] Patent: WO2005/61442, 2005, A1, . Location in patent: Page/Page column 46
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