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Chemical Structure| 240401-22-3 Chemical Structure| 240401-22-3

Structure of 240401-22-3

Chemical Structure| 240401-22-3

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Product Details of [ 240401-22-3 ]

CAS No. :240401-22-3
Formula : C6H11ClN2
M.W : 146.62
SMILES Code : N#CC1CCNCC1.[H]Cl
MDL No. :MFCD09037930
InChI Key :PKMPMUHWHIIFBJ-UHFFFAOYSA-N
Pubchem ID :22744637

Safety of [ 240401-22-3 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H319
Precautionary Statements:P264-P270-P280-P301+P310+P330-P305+P351+P338-P337+P313-P405-P501
Class:6.1
UN#:2811
Packing Group:

Computational Chemistry of [ 240401-22-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.83
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 42.27
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

35.82 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.81
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

0.93
Log Po/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.

0.42
Log Po/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

1.08
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.65

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.26
Solubility 8.07 mg/ml ; 0.055 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.14
Solubility 10.5 mg/ml ; 0.0718 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

-1.11
Solubility 11.3 mg/ml ; 0.0773 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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.62 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

0.0 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)

1.18

Application In Synthesis of [ 240401-22-3 ]

* 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 [ 240401-22-3 ]

[ 240401-22-3 ] Synthesis Path-Downstream   1~20

  • 1
  • [ 91419-52-2 ]
  • [ 240401-22-3 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In 1,4-dioxane; at 20℃; for 0.75h; Step B: TERT-BUTYL 4-CYANOPIPERIDINE-1-CARBOXYLATE (4.87g, 23. 2MMOL) was dissolved in a solution of 4N HCl/dioxane (30mL) and stirred at rt. After 45min, starting material was no longer present by TLC, and the reaction mixture was concentrated. The product was obtained as an HC1 salt.
With hydrogenchloride; In 1,4-dioxane; at 20℃; for 0.75h; Step B: tert-Butyl 4-cyanopiperidine-1-carboxylate (4.87 g, 23.2 mmol) was dissolved in a solution of 4N HCl/dioxane (30 mL) and stirred at rt. After 45 min, starting material was no longer present by TLC, and the reaction mixture was concentrated. The product was obtained as an HCl salt.
2.12 g With hydrogenchloride; In ethyl acetate; at 20℃; for 1h; To a solution of N-Boc-4-cyanopiperidine (2.62 g, 12.4 mmol) in EtOAc (10 mL) was carefully added 10 mL HCl/EtOAc. The mixture was stirred at room temperature for 1 h. The solvent was removed by reducing pressure to afford 2.12 g white solid. The filtrate was concnetrated to dryness which was used directly in the next step directly. H NMR (CD3OD) delta 3.40-3.32 (m, 2H), 3.23-3.17 (m, 3H), 2.26-2.21 (m, 2H), 2.10-2.01 (m, 2H).
With hydrogenchloride; In methanol; isopropyl alcohol; at 20℃; Intermediate 42Piperidine-4-carbonitrile hydrochloride tert-Butyl 4-cyanopiperidine-l-carboxylate (2.100 g, 9.99 mmol) in methanol (15 ml) was added with HCl in z'-PrOH(3 ml, 5-6N solution). The reaction was stirred at room temperature overnight. Solvent was removed to get 1.56 g product as HCl salt. The material was directly used for the next step reaction without further purification. IH NMR (300 MHz, MeOD) delta ppm 1.82 - 2.03 (m, 2 H) 2.04 - 2.21 (m, 2 H) 3.00 - 3.15 (m, 3 H) 3.17 - 3.32 (m, 2 H).

  • 2
  • [ 859218-87-4 ]
  • [ 240401-22-3 ]
  • 1-[4-(4-butylpiperazin-1-yl)-3-(4,4-dimethylcyclohexyl)phenyl]piperidine-4-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium t-butanolate;palladium diacetate; tri tert-butylphosphoniumtetrafluoroborate; In xylene; at 100℃; for 1h; A mixture of 1-[4-bromo-2-(4,4-dimethylcyclohexyl)phenyl]-4-butylpiperazine (50 mg, 0.123 mmol) produced in Example (57b), <strong>[240401-22-3]piperidine-4-carbonitrile hydrochloride</strong> (27 mg, 0.185 mmol), sodium t-butoxide (47 mg, 0.492 mmol), palladium(II) acetate (3 mg, 0.0123 mmol), tri-t-butylphosphonium tetrafluoroborate (11 mg, 0.0369 mmol) and xylene (1 mL) was stirred for 1 hour at an external temperature of 100 C. The reaction mixture was purified by NH silica gel column chromatography (ethyl acetate/hexane) to give 32 mg of 1-[4-(4-butylpiperazin-1-yl)-3-(4,4-dimethylcyclohexyl)phenyl]piperidine-4-carbonitrile as a colorless solid. 1H-NMR (400 MHz, CDCl3) delta: 0.94 (t, J=7.6 Hz, 3H), 0.97 (s, 3H), 1.01 (s, 3H), 1.24-1.64 (m, 12H), 1.95-2.13 (m, 4H), 2.36-2.46 (m, 2H), 2.59 (brs, 4H), 2.72-2.79 (m, 1H), 2.86 (brs, 4H), 2.91-3.05 (m, 3H), 3.31-3.41 (m, 2H), 6.72 (dd, J=8.8, 2.8 Hz, 1H), 6.84 (d, J=2.8 Hz, 1H), 7.07 (d, J=8.8 Hz, 1H).
YieldReaction ConditionsOperation in experiment
11.0 g of 1-benzyl-4-piperidinecarbonitrile was dissolved in 100 ml 1,2-dichloroethane, 7.1 ml 1-chloroethyl chloroformate was added thereto under ice-cooling. The mixture was stirred at room temperature for 15 min, and then heated under reflux for 1 hr and 20 min. After evaporating, 50 ml methanol was added thereto and it was heated under reflux for 1 hr. The reaction solution was evaporated, and the crystalline residue was washed with ethyl acetate and collected by filtration to give 8.0 g of 4-piperidinecarbonitrile hydrochloride as white crystals.
  • 4
  • [ 872-50-4 ]
  • [ 178308-63-9 ]
  • [ 240401-22-3 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; A mixture of 1.2 g of the resulting 4-piperidinecarbonitrile hydrochloride, 1.0 g 1-chloro-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine, 1.8 g diisopropylethylamine, and 10 ml 1-methyl-2-pyrrolidone was stirred at 170 C. for 2 hr and 30 min.
  • 5
  • [ 240401-22-3 ]
  • [ 594-44-5 ]
  • [ 936482-02-9 ]
YieldReaction ConditionsOperation in experiment
In a dry round bottom flask was placed <strong>[240401-22-3]4-cyanopiperidinium chloride</strong> (13, 5g, 45.4 mmol) dichloromethane (150ml) and triethylamine (18.98ml, 136 mmol). To the reaction was added dropwise ethanesulfonyl chloride (4.56 ml, 45.4 mmol) and the solution stirred 1 hour and quenched with water (100 ml). The mixture was extracted with dichloromethane (3x 50 ml) and the combined organic <n="55"/>fractions dried (MgSO4), filtered, and the solvent evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with EtOAc/Hexanes to give 1- (ethylsulfonyl)pirhoeridine-4-carbonitrile (14) as a white solid. MS 203 (M+l)
  • 6
  • [ 75-44-5 ]
  • [ 240401-22-3 ]
  • [ 1257301-09-9 ]
  • [ 1257301-10-2 ]
YieldReaction ConditionsOperation in experiment
61% 2-methylpropyl 2-[4-(2,3,4,5-tetrahydro-l,4-benzoxazepin-7-yl)phenyl]- lH-imidazole-1-carboxylate (361 mg, 0.92 mmol) was taken into dichloromethane (5 mL) followed by addition of DIPEA (0.32 mL, 1.84 mmol). The solution thus obtained was added slowly by syringe over several minutes to a solution of phosgene (20 W% in toluene, 0.49 mL, 0.93 mmol) diluted in dichloromethane (5 mL) and cooled to 0 0C. The resulting mixture was stirred for 5 minutes then allowed to warm to room temperature and concentrated. The residue was taken back into dichloromethane (5 mL) followed by addition of DIPEA (0.48 mL, 2.76 mmol) and <strong>[240401-22-3]4-cyanopiperidine hydrochloride</strong> salt (156 mg, 1.06 mmol) then stirred for 12h. The mixture was concentrated then partitioned with ethyl acetate and 10% aqueous citric acid. The organic solution was washed with brine, dried over anhydrous sodium sulfate then filtered and concentrated. The residue was purified by silica gel chromatography (100% ethyl acetate) to give 2-methylpropyl 2-(4-{4-[(4-cyanopiperidin-l-yl)carbonyl]-2,3,4,5- tetrahydro-l,4-benzoxazepin-7-yl}phenyl)-lH-imidazole-l-carboxylate (296 mg, 61 % yield) as a crystalline solid. MS (EI) for C30H33N5O4: 529 (MH+).
  • 7
  • [ 240401-22-3 ]
  • N,N'-di-BOC methyl {5-[4-(chlorocarbonyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]-1H-benzimidazol-2-yl}carbamate [ No CAS ]
  • [ 1257301-34-0 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 1h; A mixture of N,N'-di-BOC methyl {5-[4-(chlorocarbonyl)-2,3,4,5- tetrahydro-l,4-benzoxazepin-7-yl]-lH-benzimidazol-2-yl}carbamate (40 mg, 0.07 mmol), 4- cyanopiperidine hydrochloride (20 mg, 0.14 mmol), and diisoproylethylamine (0.13 mL, 0.14 mmol), in dichloromethane (2 mL) was stirred at room temperature for one hour. The mixture was concentrated and purified directly by silica gel chromatography (0-15% methanol- dichlomethane) to give N,N'-di-BOC methyl (6-{4-[(4-cyanopiperidin-l-yl)carbonyl]- 2,3 ,4,5-tetrahydro- 1 ,4-benzoxazepin-7-yl} - 1 H-benzimidazol-2-yl)carbamate as an amorphous residue.
  • 8
  • [ 240401-22-3 ]
  • [ 337909-10-1 ]
  • C19H21N3O3 [ No CAS ]
  • 9
  • [ 240401-22-3 ]
  • [ 337909-10-1 ]
  • [ 1181964-72-6 ]
  • 10
  • [ 240401-22-3 ]
  • C12H11FN2O [ No CAS ]
  • C18H21FN4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
3.3 g To a stirred suspension of compound Int 1-5 (2.12g) in 30 mL of dry THF was added compound Int 1-4 (2.7 g, 12.4 mmol), excess Ti(OPr)4, MgS04 andNa2C03. The mixture was stirred at 70C oil bath for 4 h. The mixture was cooled to room temperature, then to the stirring mixture suspension was added excess NaBH(OAc)3 and stirred for 2h. The mixture was filtrated and concentrated. The residue was purified by column to afford 3.3 g yellow solid. H NMR (CDCI3 ) delta 7.65 (s, 1H), 7.01-6.98 (m, 4H), 6.89 (s, 1H), 5.62 (q, J=6.8 Hz, 1H), 2.57-2.49 (m, 4H), 2.23-2.08 (m, 2H), 1.83 (d, J=8.4 Hz, 2H), 1.79 (d, J=7.2 Hz, 3H), 1.76-1.70 (m, 3H). MS (ESI) m/z(M+l): 313.
  • 11
  • [ 240401-22-3 ]
  • C12H11FN2O [ No CAS ]
  • (R)-4-ethyl-1-((1-(1-(4-fluorophenyl)ethyl)-1H-imidazol-5-yl)methyl)piperidine-4-carbonitrile [ No CAS ]
  • 12
  • [ 240401-22-3 ]
  • methyl 1-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-4-carboxylate [ No CAS ]
  • [ 76-05-1 ]
  • 1-(2-(1-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2-oxoethyl)piperidine-4-carbonitrile trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% Example 12-10 l-(2-(l-(4-Fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-lH-pyrazolo[3,4-c]pyridin- 6(7H)-yl)-2-oxoethyl)piperidine-4-carbonitrile TFA salt To a solution of 2-chloro-l-(l-(4-fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro- 1H- pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone (Example 12-1, step 1) (100 mg, 0.267 mmol) and <strong>[240401-22-3]piperidine-4-carbonitrile hydrochloride</strong> (78 mg, 0.533 mmol) in CH3CN (8 mL) was added Cs2C03 (174 mg, 0.533mmol). The mixture was stirred at rt for 16 h. The reaction mixture was filtered and the filtrate was concentrated. The residue was purified by reverse phase HPLC (MeCN and H20 with 0.05% TFA as mobile phase) to give l-(2-(l-(4- fluorobenzyl)-3-(trifluoromethyl)-4,5-dihydro-lH-pyrazolo[3,4-c]pyridin-6(7H)-yl)-2- oxoethyl)piperidine-4-carbonitrie trifluoroacetate salt as a yellow solid (60 mg, yield 50%). 1H NMR (400 MHz, Methanol-d4) delta: 7.32-7.26 (m, 2H), 7.15-7.08 (m, 2H), 5.37- 5.36 (m, 2H), 4.67-4.52 (m, 2H), 4.40-4.32 (m, 2H), 3.87-3.61 (m, 4H), 3.52-3.35 (m, 1H), 3.24-2.91 (m, 2H), 2.83-2.71 (m, 2H), 2.29-2.20 (m, 4H); LCMS (ESI) m/z 450.0 [M+H]+
  • 13
  • [ 240401-22-3 ]
  • [ 31309-08-7 ]
  • C12H11N5O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 60℃; (1) <strong>[240401-22-3]4-cyanopiperidine hydrochloride</strong> (587mg) to a suspension of N- dimethylformamide, potassium carbonate (1.1g) was added to 2-chloro-5-nitro-nicotinic acid nitrile (609mg) under ice-cooling and, 60 It was stirred in. After the reaction, it cooled to room temperature and, after addition of water, the precipitated solid was collected by filtration.
  • 14
  • [ 240401-22-3 ]
  • 1-(4-chlorophenyl)-N-[5-cyano-6-(4-cyanopiperidine-1-yl)pyridin-3-yl]-1H-pyrazol-4-carboxamide [ No CAS ]
  • 15
  • [ 240401-22-3 ]
  • 1-(5-amino-3-cyanopyridin-2-yl)-4-cyanopiperidine [ No CAS ]
  • 16
  • [ 39546-32-2 ]
  • [ 240401-22-3 ]
YieldReaction ConditionsOperation in experiment
86.5% With thionyl chloride; N,N-dibutylformamide; In toluene; at 20℃; for 18h; 11.9 g [75.7 mmol] of dibutylformamide (99%) were added to a suspension of 10 g [75.7 mmol] of isonipecotamide (97%) in 50 ml of toluene at 20C over 5 minutes. After 5 minutes, the addition of 18.91 g [158.9 mmol] of thionyl chloride at 20C was initiated. This addition required 45 minutes in which the temperature was maintained constantly at 20C. After the end of the addition, the mixture was stirred at 20C for a further 18 hours. The suspension was filtered and the filter residue was washed with toluene. After drying there remained 9.63 g of a colourless solid. Analysis by GC against a reference standard following silylation gave a 4-cyanopiperidine hydrochloride content of 99.7% (w/w). A yield of 86.5%) of theory is calculated therefrom.
  • 17
  • [ 240401-22-3 ]
  • [ 32779-36-5 ]
  • 1-(5-bromopyrimidin-2-yl)piperidine-3-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 80℃; for 24h; General procedure: A solution of 5-bromo-2-chloropyrimidine (CAS: 32779-36-5, 300 mg, 1.55 equiv), 3-cyanopiperidine hydrochloride (CAS:828300-57-8, 250 mg, 1.7 mmol) and DIPEA (567 muL, 3.3 mmol) in acetonitrile (3 mL) was heated at 80 C. for 4 hours. 3-Cyanopiperidine hydrochloride (CAS:828300-57-8, 125 mg, 0.85 mmol) and DIPEA (567 muL, 3.3 mmol) were again added, and the stirring at 80 C. was continued for 20 hours. The reaction mixture was diluted with DCM and washed with water. The organic phase was separated using a phase separator and concentrated under reduced pressure. The residue was purified by flash column chromatography eluting with n-heptane/ethyl acetate to give the titled compound.
  • 18
  • [ 240401-22-3 ]
  • piperidine-4-carbothioamide hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With hydrogen sulfide; dibutylamine; In ethanol; at 60℃; under 3000.3 Torr; for 17h; General procedure: 50 ml of ethanol, 15 g of <strong>[240401-22-3]4-cyanopiperidine hydrochloride</strong> (102.2 mmol) and 0.52 g of triethylamine (5.1 mmol) are heated to 60C in a 250 ml pressure reactor. Subsequently, hydrogen sulphide is introduced into the reactor, such that there is a constant gauge pressure of 4 bar. After 5 hours, no further hydrogen sulphide is introduced, and the reaction mixture is stirred at 60C for a further 12 hours and then cooled down to 20C. Excess hydrogen sulphide is discharged via a chlorine bleach scrubber, then the reaction mixture is cooled down further to 10C and the gas space of the reactor is purged with nitrogen for 15 minutes. The solids present in the reactor are subsequently filtered off with suction using a glass suction filter, washed once more with a little ethanol (25 ml) and dried by suction. On completion of drying at 40C under reduced pressure, 16.8 g (92.9 mmol, 91% of theory) of the desired piperidine-4-carbothioamide hydrochloride (I) are obtained in a purity of 99%
  • 19
  • [ 240401-22-3 ]
  • 2-(6-chloropyridin-3-yl)-1,3-benzoxazole [ No CAS ]
  • 1-[5-(1,3-benzoxazol-2-yl)pyridin-2-yl]piperidine-4-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With triethylamine; In methanol; at 150℃; for 3h;Microwave irradiation; Inert atmosphere; General procedure: A chloro substituted pyridine/pyrimidine/pyrazine (1 equivalent) and a substituted piperidine (1.5-4 equivalents, for example 3 equivalents) or salt thereof were dissolved or slurried in a suitable solvent (for example NMP, DMF or an alcohol (ethanol or methanol)) and subjected to heat either by an oil bath or using the microwave at a temperature between 120 - 160 C for 60 min to overnight (for example 90 min). Where the substituted piperidine is in the form of a HCI salt, an excess of triethylamine (TEA) is added. (0275) The reaction was routinely run in methanol and the product was isolated, upon cooling of the reaction mixture, by cooling the solution and washing with cold methanol. In the cases where the product was impure then chromatography was used to isolate the pure product.
  • 20
  • [ 240401-22-3 ]
  • [ 201230-82-2 ]
  • 1,1'-carbonylbis(piperidine-4-carbonitrile) [ No CAS ]
 

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Related Functional Groups of
[ 240401-22-3 ]

Nitriles

Chemical Structure| 948894-26-6

A337465 [948894-26-6]

4-Methylpiperidine-4-carbonitrile hydrochloride

Similarity: 0.96

Chemical Structure| 1199773-75-5

A145824 [1199773-75-5]

Piperidine-3-carbonitrile hydrochloride

Similarity: 0.92

Chemical Structure| 26458-78-6

A274566 [26458-78-6]

Quinuclidine-4-carbonitrile

Similarity: 0.88

Chemical Structure| 1153950-49-2

A201195 [1153950-49-2]

(S)-Pyrrolidine-3-carbonitrile hydrochloride

Similarity: 0.81

Chemical Structure| 1187930-86-4

A274321 [1187930-86-4]

Pyrrolidine-3-carbonitrile hydrochloride

Similarity: 0.81

Related Parent Nucleus of
[ 240401-22-3 ]

Piperidines

Chemical Structure| 948894-26-6

A337465 [948894-26-6]

4-Methylpiperidine-4-carbonitrile hydrochloride

Similarity: 0.96

Chemical Structure| 1199773-75-5

A145824 [1199773-75-5]

Piperidine-3-carbonitrile hydrochloride

Similarity: 0.92

Chemical Structure| 78619-84-8

A111182 [78619-84-8]

4,4'-Bipiperidine dihydrochloride

Similarity: 0.78

Chemical Structure| 452331-68-9

A130463 [452331-68-9]

4-Propylpiperidine hydrochloride

Similarity: 0.78

Chemical Structure| 372195-85-2

A329883 [372195-85-2]

4-Butylpiperidine hydrochloride

Similarity: 0.78