19733-56-3|4-(Piperidin-3-yl)aniline| Ambeed

Structure of 19733-56-3

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Quality Control of [ 19733-56-3 ] Purity: 95% SDS Specification

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Product Details of [ 19733-56-3 ]

CAS No. :	19733-56-3
Formula :	C₁₁H₁₆N₂
M.W :	176.26
SMILES Code :	NC1=CC=C(C2CNCCC2)C=C1
MDL No. :	MFCD11047425
InChI Key :	COUOFYDJUDASPJ-UHFFFAOYSA-N
Pubchem ID :	24904214

Safety of [ 19733-56-3 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 19733-56-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	6
Fraction Csp3	0.45
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	2.0
Molar Refractivity	59.64
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	38.05 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.96
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.35
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.36
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.73
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.02
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.68

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.06
Solubility	1.54 mg/ml ; 0.00873 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.75
Solubility	3.13 mg/ml ; 0.0177 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.24
Solubility	0.1 mg/ml ; 0.00057 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.42 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.69

Application In Synthesis of [ 19733-56-3 ]

* 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 [ 19733-56-3 ]

[ 19733-56-3 ] Synthesis Path-Downstream 1~36

2
[ 19733-56-3 ]
[ 2743-38-6 ]
(3S)-3-(4-aminophenyl)-piperidine O,O'-dibenzoyl-L-tartrate [ No CAS ]
(3R)-3-(4-aminophenyl)-piperidine O,O'-dibenzoyl-L-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;Resolution of racemate;Purification / work up;	EXAMPLE 1; (3.SV3-{4-[7-(Aminocarbonyl)-2H-indazol-2-yllphenvUpiperidinium 4- methylbenzenesulfonate (D4); Step 1: tert-butyI(3S)-3-[4-({(I£H3-(methoxycarbonyl)-2- nitrophenyl]methylene}amino)phenyl]piperidine-l-carboxylate (Dl); (Dl) was prepared from Example A, A3 and tert-butyl (35)-3-(4- aminophenyl)piperidine-l-carboxylate (prepared by the resolution of 3-(4-aminophenyl)- piperidine with 2 equivalents of L-Dibenzoyl tartaric acid in MeOH and subsequent Boc- protection) as described in Example B, Bl.

References: [1]Patent: WO2009/87381,2009,A1 .Location in patent: Page/Page column 38.

3
[ 4282-46-6 ]
[ 19733-56-3 ]

Yield	Reaction Conditions	Operation in experiment
80.7%	With hydrogenchloride; platinum(IV) oxide; hydrogen; In methanol; at 10 - 40℃; under 750.075 - 3000.3 Torr; for 18h;	(20.0 g), methanol (180 mL) and 0.1 m hydrochloric acid are added to a hydrogenation reaction, and the reaction is carried out in the same manner as in the literature (Org. Process Res. Dev.2011, 15, 831-840). Specifically, 3- (4-nitrophenyl) Kettle, then add PtO2(2 g) was evacuated and the nitrogen was exchanged and the reaction mixture was cooled to 10 C2The reaction mixture was heated to 40 C, stirred for 18 h, cooled to room temperature, neutralized with sodium hydroxide solution, extracted with isopropyl acetate, concentrated, and added to the reaction mixture. The amount of N- (4- (pyridin-3-yl) phenyl) hydroxylamine was 4.2%

References: [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 7170 - 7185.
[2]Patent: CN106432054,2017,A .Location in patent: Paragraph 0045; 0046.
[3]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[4]Patent: CN106432055,2017,A .
[5]Patent: CN106749181,2017,A .

4
[ 87-69-4 ]
[ 19733-56-3 ]
[ 1196713-22-0 ]
C₄H₆O₆*C₁₁H₁₆N₂ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 7170 - 7185.

5
[ 34619-03-9 ]
[ 19733-56-3 ]
[ 875798-79-1 ]

References: [1]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.

6
[ 19733-56-3 ]
[ 1038915-64-8 ]

References: [1]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[2]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[3]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[4]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[5]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[6]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[7]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[8]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[9]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[10]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[11]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[12]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[13]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[14]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[15]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[16]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[17]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[18]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[19]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[20]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[21]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[22]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[23]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[24]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[25]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[26]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[27]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[28]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[29]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[30]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[31]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[32]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[33]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[34]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[35]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[36]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[37]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[38]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[39]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[40]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[41]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[42]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.

7
[ 19733-56-3 ]
[ 1171197-20-8 ]

References: [1]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[2]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[3]Patent: CN106749181,2017,A .

8
[ 19733-56-3 ]
[ 1171197-20-8 ]
[ 1263284-59-8 ]

References: [1]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.

9
[ 19733-56-3 ]
[ 1196713-67-3 ]

10
[ 19733-56-3 ]
[ 1038916-11-8 ]

11
[ 19733-56-3 ]
[ 1196713-21-9 ]

Yield	Reaction Conditions	Operation in experiment
8.7 g	With L-Tartaric acid; In acetonitrile; at 10℃;Reflux;	A solution of compound 7 (25 g, 0.13 mol) was added 110 mL of acetonitrile,After heating to reflux,L-tartaric acid (15.2 g, 0.104 mol) was added in portions and after refluxing for 2 hours,Slowly down to 10 C (1.5 hours)And stirred at this temperature overnight. After filtering off the solid, 85 mL of ethanol was added to the solid,After heating to reflux and stirring for 1 hour,Then down to room temperature crystallization 8 hours, filter out the solid,And dried under reduced pressure (45 C) to give 16.4 g of an off-white solid,To the resulting solid was added 50 mL of ethyl acetate,And 30 mL of 0.1 M sodium hydroxide solution was added,After stirring for 20 minutes, the mixture was extracted twice with ethyl acetate (2 * 50 mL)The organic phase was washed once with saturated citric acid (100 mL) and the organic phase was dried over anhydrous sodium sulfate,The organic phase was distilled off to give 8.7 g of a pale yellow oil, 60 mL of dichloromethane was added,Di-tert-butyl dicarbonate (10.8 g, 0.05 mol)Triethylamine (5.70 g, 0.057 mol) was added,DMAP (0.460 g, 3.80 mmol) and reacted at room temperature for 8 hours. The reaction solution was washed with saturated sodium bicarbonate,Dried over anhydrous sodium sulfate and the organic phase was distilled off to give 12.1 g of a pale yellow solid

References: [1]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.
[2]Patent: CN106749181,2017,A .Location in patent: Paragraph 0051; 0052.

12
[ 19733-56-3 ]
C₂₅H₂₉N₅O₄ [ No CAS ]

13
[ 19733-56-3 ]
[ 1038916-08-3 ]

14
[ 19733-56-3 ]
C₂₁H₃₂N₂O₄ [ No CAS ]

15
[ 19733-56-3 ]
C₂₉H₃₅N₃O₆ [ No CAS ]

16
[ 19733-56-3 ]
[ 1312106-32-3 ]

17
[ 19733-56-3 ]
[ 2743-38-6 ]
C₁₁H₁₆N₂*2C₁₈H₁₄O₈ [ No CAS ]
C₁₁H₁₆N₂*C₁₈H₁₄O₈ [ No CAS ]

References: [1]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.

18
[ 19733-56-3 ]
[ 2743-38-6 ]
C₁₁H₁₆N₂*C₁₈H₁₄O₈ [ No CAS ]

References: [1]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.

19
[ 19733-56-3 ]
[ 2743-38-6 ]
C₁₁H₁₆N₂*2C₁₈H₁₄O₈ [ No CAS ]

References: [1]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.

20
[ 1692-25-7 ]
[ 19733-56-3 ]

References: [1]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.

21
[ 586-78-7 ]
[ 19733-56-3 ]

References: [1]Organic Process Research and Development,2011,vol. 15,p. 831 - 840.

22
1-benzyl-3-(4-nitrophenyl)pyridinium bromide [ No CAS ]
[ 19733-56-3 ]

Yield	Reaction Conditions	Operation in experiment
96%	With 5%-palladium/activated carbon; hydrogen; acetic acid; at 30℃; under 1125.11 - 1500.15 Torr; for 12h;	186.0 g of 1-benzyl-3- (4-nitrophenyl) pyridinium bromide was dissolved in 1.0 L of acetic acid,Adding 15 g of 5% palladium on carbon, replacing it with nitrogen for 3 times, replacing 5 times with hydrogen, introducing 2 bar of hydrogen, slowly warming to 30 C, catalyzing hydrogen reaction for more than 12 h under 1.5 bar pressure, recovering catalyst by filtration,To the residue was added 2 L of water, adjusted to pH 14 with sodium hydroxide solution, extracted with ethyl acetate (500 mL x 3 times)The organic phases were combined and concentrated under reduced pressure to give 84.7 g of a pale yellow solid, 96.0% yield, 99.14% HPLC purity,impurity N- (4- (pyridin-3-yl) phenyl) hydroxylamine Not detected, N- (4- (piperidin-3-yl) phenyl) acetamide Not detected.
9.3 g		Compound 3 (43.0 g, 0.12 mol) was added to 130 mL of methanol,The reaction solution was cooled to 3-5 C,Sodium borohydride (18.2 g, 0.48 mol) was added and the addition was complete,After stirring at this temperature for 30 minutes,The reaction was carried out at room temperature for 8 hours. After most of the methanol was distilled off under reduced pressure, 110 mL of water was added,(2 * 150 mL) was extracted with ethyl acetate and the organic phase was dried over anhydrous sodium sulfate. The organic phase was evaporated to dryness to give 22.8 g of a pale yellow solid.; In the autoclave,To a mixture of compounds 5, 6 (19.0 g, 0.065 mol) was added 110 mL of methanol,Add acetic acid 30mL,Adding 1.5 g of palladium hydroxide, introducing hydrogen gas,After the reaction at 12 atmospheres for 24 hours, after the reaction is completed,The solid was filtered off and most of the methanol in the filtrate was distilled off under reduced pressure. 130 mL of 1 mL of sodium hydroxide solution was added,After stirring for 20 minutes, the mixture was extracted twice with ethyl acetate (2 * 100 mL) and the organic phase was washed once with saturated citric acid (100 mL)The organic phase was dried over anhydrous sodium sulfate and the organic phase was evaporated to dryness to give 9.3 g of a pale yellow solid.

References: [1]Patent: CN106432055,2017,A .Location in patent: Paragraph 0031; 0032-0038; 0041; 0042; 0045; 0046.
[2]Patent: CN106749181,2017,A .Location in patent: Paragraph 0045; 0046; 0049; 0050.

23
1-benzyl-3-(4-nitrophenyl)pyridinium chloride [ No CAS ]
[ 19733-56-3 ]

Yield	Reaction Conditions	Operation in experiment
1.61 g	With 5%-palladium/activated carbon; hydrogen; acetic acid; at 37℃; under 1500.15 Torr; for 12h;	3.17 g of 1-benzyl-3- (4-nitrophenyl) pyridinium chloride was dissolved in 20 mL of acetic acid (the organic solvent wasAcetic acid, ethanol, methanol, ethyl acetate), adding 5% palladium carbon 0.2g, nitrogen replacement 3 times, hydrogen replacement 5 times, through 2bar hydrogen, slowly warming to 37 , 2bar pressure catalytic hydrogen reaction 12h or more,The catalyst was recovered by filtration, the solvent was recovered under reduced pressure, and 20 mL of water was added to the residue,Adjusted to pH 14 with sodium hydroxide solution, extracted with ethyl acetate (20 mL x 3 times), combined with organic phase,Concentrated under reduced pressure to give 1.61 g as a pale yellow solid, HPLC purity 98.60%Impurities N- (4- (pyridin-3-yl) phenyl) acetamide Not detected, N- (4- (piperidin-3-yl).

References: [1]Patent: CN106432055,2017,A .Location in patent: Paragraph 0049; 0050; 0053; 0054.

24
N-allyl-3-(4-nitrophenyl)pyridine quaternary ammonium salt [ No CAS ]
[ 19733-56-3 ]

Yield	Reaction Conditions	Operation in experiment
96%	With sodium tetrahydroborate; zinc(II) chloride; In tetrahydrofuran; at 20℃; for 3.5h;Inert atmosphere;	32.1 g (100 mmol) of N-allyl-3- (4-nitrophenyl) pyridine quaternary ammonium salt and 6.8 g (50 mmol) of zinc chloride were added to a reaction vessel equipped with THF under nitrogen atmosphere to stir 10 ~ 20min,6.9 g (98%, 180 mmol) of sodium borohydride was added thereto at a temperature of 20 C for 3.5 h, and the reaction solution was concentrated to 1/3 to 1/4,Into the ice water,Dilute hydrochloric acid quenching, and then adjust the pH to 10 ~ 12 with ethyl acetate, ethyl acetate extraction, combined organic phase,And concentrated under reduced pressure to give 16.9 g of 4- (piperidin-3-yl) aniline in 96% yield.

References: [1]Patent: CN106432054,2017,A .Location in patent: Paragraph 0032; 0033; 0034; 0035; 0036; 0037; 0038; 0039-40.

25
[ 19733-56-3 ]
[ 1038915-60-4 ]

References: [1]Patent: CN106749181,2017,A .
[2]Patent: CN106749180,2017,A .

26
[ 87-69-4 ]
[ 19733-56-3 ]
4-(3-piperidinyl)aniline tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	In ethanol; for 2h;Reflux;	The free amine product of the previous step 1 was dissolved in 300 ml of absolute ethanol,(L) -tartaric acid ethanol solution (28ml, 0.028mol) was added within 5 minutes. After the addition was completed, the reaction mixture was refluxed for 2 hours. The mixture was slowly cooled down and the crystals were lyophilized to be completely crystallized and filtered. The cake was washed with anhydrous ethanol 100ml x 2) and dried to give 5.9g light yellow solid in 60% yield.

References: [1]Patent: CN106883166,2017,A .Location in patent: Paragraph 0036; 0037.

27
[ 2945-08-6 ]
[ 19733-56-3 ]

References: [1]Patent: CN106883166,2017,A .

28
methyl 4-cyano-2-(4-nitrophenyl)butyrate [ No CAS ]
[ 19733-56-3 ]

References: [1]Patent: CN106883166,2017,A .

29
3-(4-aminophenyl)piperidin-2-one [ No CAS ]
[ 19733-56-3 ]

Yield	Reaction Conditions	Operation in experiment
72%	With borane-THF; In tetrahydrofuran; for 16h;Reflux;	The compound 5 obtained in the previous step was dissolved in 150 ml of dry tetrahydrofuran and 158.4 ml (1 mol / L, 0.158 mol) of borane-tetrahydrofuran complex was slowly added at room temperature. After addition was completed, the temperature was slowly raised to reflux, and the reaction was carried out for 16 hours. Then, the reaction solution was cooled in an ice bath and 10 ml of concentrated hydrochloric acid was slowly added, followed by further warming for 2 hours. After the reaction was over, the reaction solution was adjusted to pH 13-14 with 2 mol / L aqueous sodium hydroxide and extracted with ethyl acetate (150 ml x 5). The organic phases were combined, washed with saturated brine (150 ml x 2) Sodium was dried and concentrated under reduced pressure to give 4.88 g of white solid with a yield of 72%

References: [1]Patent: CN106883166,2017,A .Location in patent: Paragraph 0034; 0035.

30
[ 104-03-0 ]
[ 19733-56-3 ]

References: [1]Patent: CN106883166,2017,A .

31
[ 40114-49-6 ]
[ 358-23-6 ]
[ 171364-83-3 ]
[ 19733-56-3 ]

Yield	Reaction Conditions	Operation in experiment
9.3 g		Example 1 Compound 3 (36.0 g, 0.19 mol) was dissolved in 190 mL of methylene chloride under a nitrogen atmosphere,Diisopropylethylamine (27.0 g, 0.21 mol) was added and the temperature was lowered to -60 C. Trifluoromethanesulfonic anhydride (59.2 g,0.21 mol) was added and reacted at this temperature. After the reaction, water was added, the temperature was raised to room temperature, the mixture was extracted with ethyl acetate, and saturated sodium bicarbonateAfter washing and drying of the organic phase, the solvent was distilled off under reduced pressure to give 44.5 g of compound 3 as a light yellow solid.Example 2 A mixture of compound 3 (39.0 g, 0.12 p-nitrophenyl boronate mol) under nitrogen was added 130 mL of tetrahydrofuranAfter dissolution, (31.4 g, 0.13 mol), palladium tetrakistriphenylphosphine (6.9 g, 6.0 mmol), potassium carbonate(33.1 g, 0.13 mol) and heated to reflux temperature and reacted at this temperature for 8 hours, after which time the system was lowered to roomThe reaction solution was filtered through celite and the filtrate was evaporated under reduced pressure to a partial solvent, the crystals precipitated at low temperature, filtered to give a mixture of compounds 5,6The compound was 37.5 g as a light brown solid.Example 3 In an autoclave, 110 mL of methanol was added to a mixture of compounds 5 and 6 (19.0 g, 0.065 mol), 30 mL of acetic acid was added, 1.5 g of palladium hydroxide was added,After the introduction of hydrogen, after 12 at atmospheric pressure for 24 hours, after the reaction,The solid was filtered off and most of the methanol in the filtrate was evaporated under reduced pressure. 130 mL of 1 mL sodium hydroxide solution was added and the mixture was stirred for 20 minutes.The mixture was extracted twice with ethyl acetate (2 * 100 mL), the organic phase was washed once with saturated citric acid (100 mL) and the organic phase was washed with anhydrous sodium sulfateDrying, the organic phase pressure steaming to give a pale yellow solid 9.3g.

References: [1]Patent: CN106749180,2017,A .Location in patent: Paragraph 0042; 0043; 0044; 0045; 0046; 0047.

32
[ 87-69-4 ]
[ 24424-99-5 ]
[ 19733-56-3 ]
[ 1171197-20-8 ]

Yield	Reaction Conditions	Operation in experiment
12.1 g		110 mL of acetonitrile was added to Compound 7 (25 g, 0.13 mol), heated to reflux,L-tartaric acid (15.2 g, 0.104 mol) was added portionwise and after refluxing for 2 hours after addition,Slowly reduced to 10 C (within 1.5 hours) and stirred at this temperature overnight. After filtering off the solids,The solid was added with ethanol 85mL, heated to reflux and stirred for 1 hour,After cooling to room temperature crystallization 8 hours, filtered off the solid,And dried under reduced pressure (45 C) to give 16.4g as an off-white solid,The obtained solid was added with 50 mL of ethyl acetate, and 30 mL of 0.1 M sodium hydroxide solution was added thereto,After stirring for 20 minutes, the mixture was extracted twice with ethyl acetate (2 * 50 mL)The organic phase was washed once with saturated citric acid (100 mL), the organic phase was dried over anhydrous sodium sulfate,The organic phase was evaporated under pressure to give a pale yellow oil 8.7g, dichloromethane was added 60mL,Di-tert-butyl dicarbonate(10.8 g, 0.05 mol). Triethylamine (5.70 g, 0.057 mol) and DMAP (0.460 g, 3.80 mmol) were added and the mixture was reacted at room temperature for 8 hours. The reaction mixture was washed with saturated bicarbonate , Dried over anhydrous sodium sulphate and the organic phase was autoclaved to give 12.1 g of light yellow solid.

References: [1]Patent: CN106749180,2017,A .Location in patent: Paragraph 0048; 0049.

33
[ 30698-33-0 ]
[ 19733-56-3 ]

References: [1]Patent: WO2019/36441,2019,A1 .
[2]Patent: WO2019/36441,2019,A1 .
[3]Patent: WO2019/36441,2019,A1 .
[4]Patent: WO2019/36441,2019,A1 .
[5]Patent: WO2019/36441,2019,A1 .

34
dimethyl 2-cyano-2-(4-nitrophenyl)pentanedioate [ No CAS ]
[ 19733-56-3 ]

References: [1]Patent: WO2019/36441,2019,A1 .
[2]Patent: WO2019/36441,2019,A1 .
[3]Patent: WO2019/36441,2019,A1 .

35
[ 119023-00-6 ]
[ 19733-56-3 ]

References: [1]Patent: WO2019/36441,2019,A1 .
[2]Patent: WO2019/36441,2019,A1 .

36
5-(4-aminophenyl)piperidin-2-one [ No CAS ]
[ 19733-56-3 ]

Yield	Reaction Conditions	Operation in experiment
12.1 g	With sodium tetrahydroborate; boron trifluoride diethyl etherate; In tetrahydrofuran; at 0 - 10℃;	To the suspension of 5-(4-aminophenyl) piperidin-2-one (Compound 15) (15 g) in THF (150 mL), NaBH4 (8.95 g) and BF3.etherate (3.357 g) was charged at 0-10C. The reaction mixture was maintained for 4-6 h or until HPLC/TLC analysis indicated completion of reaction. After completion of reaction, reactions mass was cooled to 0-5C and slowly quenched with 5M HCl solution (100 mL). The reaction mass was heated to 60-65C and maintained for 1 h. Reaction mass was cooled to 0-10C and basified with 5M NaOH solution till pH >13.0 . THF was distilled off under vacuum at 45-50C and residue was extracted with isopropyl acetate (75 mL). Organic layer was distilled off under vacuum at 50-55C to afford the titled compound (Yield: 12.10 g; HPLC Purity: 95.66%).

References: [1]Patent: WO2019/36441,2019,A1 .Location in patent: Paragraph 00199.

Historical Records

Technical Information

• Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chan-Lam Coupling Reaction • Hydride Reductions • Leuckart-Wallach Reaction • Mannich Reaction • Petasis Reaction • Preparation of Amines • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Specialized Acylation Reagents-Vilsmeier Reagent • Ugi Reaction

Related Functional Groups of
[ 19733-56-3 ]

Aryls

A293511 [113310-52-4]

4-(Piperidin-4-yl)aniline

Similarity: 0.95

A269838 [454482-12-3]

4-(1-Methylpiperidin-4-yl)aniline

Similarity: 0.90

A598653 [474538-99-3]

1'-Benzylspiro[indoline-3,4'-piperidine]

Similarity: 0.83

A231594 [3973-62-4]

3-Phenylpiperidine

Similarity: 0.82

A323022 [430461-56-6]

(R)-3-Phenylpiperidine

Similarity: 0.82

Amines

A293511 [113310-52-4]

4-(Piperidin-4-yl)aniline

Similarity: 0.95

A269838 [454482-12-3]

4-(1-Methylpiperidin-4-yl)aniline

Similarity: 0.90

A150486 [29608-05-7]

4-(Piperidin-1-ylmethyl)aniline

Similarity: 0.79

A558149 [115955-90-3]

1,2,3,4-Tetrahydroisoquinolin-5-amine

Similarity: 0.79

A235540 [55751-54-7]

2-(sec-Butyl)aniline

Similarity: 0.78

Related Parent Nucleus of
[ 19733-56-3 ]

Piperidines

A293511 [113310-52-4]

4-(Piperidin-4-yl)aniline

Similarity: 0.95

A269838 [454482-12-3]

4-(1-Methylpiperidin-4-yl)aniline

Similarity: 0.90

A284785 [69584-91-4]

1'-Methylspiro[indoline-3,4'-piperidine]

Similarity: 0.83

A598653 [474538-99-3]

1'-Benzylspiro[indoline-3,4'-piperidine]

Similarity: 0.83

A323022 [430461-56-6]

(R)-3-Phenylpiperidine

Similarity: 0.82

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CAS No.: 19733-56-3

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