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Chemical Structure| 919354-20-4 Chemical Structure| 919354-20-4

Structure of 919354-20-4

Chemical Structure| 919354-20-4

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Product Details of [ 919354-20-4 ]

CAS No. :919354-20-4
Formula : C7H14ClNO2
M.W : 179.64
SMILES Code : O=C(C1(C)CCNCC1)O.[H]Cl
MDL No. :MFCD18207802
InChI Key :GGMOJYOORZQAFB-UHFFFAOYSA-N
Pubchem ID :51000379

Safety of [ 919354-20-4 ]

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

Computational Chemistry of [ 919354-20-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 0
Fraction Csp3 0.86
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 48.84
TPSA ?

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

49.33 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

-1.3
Log Po/w (WLOGP)?

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

0.88
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.

0.69
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

0.86
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.23

Water Solubility

Log S (ESOL):?

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

-0.07
Solubility 153.0 mg/ml ; 0.854 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.

0.76
Solubility 1040.0 mg/ml ; 5.78 mol/l
Class?

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

Highly 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

-1.04
Solubility 16.2 mg/ml ; 0.0902 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.

-8.32 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)

1.19

Application In Synthesis of [ 919354-20-4 ]

* 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.

  • Downstream synthetic route of [ 919354-20-4 ]

[ 919354-20-4 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 919354-20-4 ]
  • [ 64119-42-2 ]
  • [ 898228-16-5 ]
YieldReaction ConditionsOperation in experiment
43% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20.0℃; (e) 1-[3-Cyano -5-(ethoxycarbonyl) -6-methylpyridin-2 -yl] -4-methylpiperidine -4- carboxylic acid; Ethyl 6-chloro-5-cyano-2-methylnicotinate (0.28 g, 1.3 mmol) and 4-methylpiperidine-4- carboxylic acid hydrochloride (0.34 g, 1.9 mmol) were suspended in DMF (20 mL) and DIPEA (1.1 mL, 6.3 mmol) was added. The reaction mixture was stirred at r.t until complete consumption of the starting materieal was observed by HPLC analysis. The reaction mixture was diluted with EtOAc (100 mL) and washed with saturated NH4Cl (70 mL), water (2 X 70 mL) and brine (50 mL). The organics were dried (Mg5O4) and concentrated under reduced pressure to afford the crude material. Flash column chromatography (1:3 EtOAc/hexanes, 0.5 % AcOH to 1:2 EtOAc/hexanes, 0.5 % AcOH) gave 1-[3-cyano-5-(ethoxycarbonyl)-6- methylpy?din-2-yl]-4-methylpiperidine-4-carboxylic acid as a solid. Yield: 0.179 g (43%). 1H NMR (400 MHz, DM5O- d6): 6 1.20 (3H, s), 1.30 (3H, t, J= 7.1Hz), 1.44-1.54 (2H, m), 2.02-2.11 (2H, m), 2.63 (3H, s), 3.39-3.48 (2H, m), 4.15-4.29 (4H, m), 8.32 (1H, s), 12.52 (1H, br s). M5 m/z: 332 (M+l).
  • 2
  • [ 892493-16-2 ]
  • [ 919354-20-4 ]
YieldReaction ConditionsOperation in experiment
(d) 4-Methylpiperidine-4-carboxylic acid hydrochloride; Methyl 4-methylpiperidine-4-carboxylate (0.300 g, 1.9 mmol) was suspended in THF (30 mL) and potassium trimethylsilanolate (2.4 g, 19 mmol) was added. The system was heated at reflux overnight and then cooled to r.t. 4 M HCl in 1,4-dioxane (12 mL, 48 mmol) was added and the system concentrated under reduced pressure to afford crude 4-methylpiperidine-4- carboxylic acid hydrochloride as a solid, which was used without further purification.
  • 3
  • [ 189321-63-9 ]
  • [ 919354-20-4 ]
YieldReaction ConditionsOperation in experiment
100% With hydrogenchloride; In 1,4-dioxane; at 20.0℃; for 2.0h; A. Preparation of 4-methylpiperidine 4-carboxylic acid. 1-(tert-Butoxycarbonyl)-4-methylpiperidine-4-carboxylic acid (0.500 g, 2.06 mmol) was treated with 4 M HCl in dioxane (10 mL) for 2 hours at room temperature to afford the title compound (0.294 g, 100%) as the hydrochloride salt. MS (ES+) [M+H]+=144.0.
  • 4
  • [ 919354-20-4 ]
  • [ 1618-36-6 ]
  • [ 1192189-30-2 ]
YieldReaction ConditionsOperation in experiment
75% With triethylamine; In isopropyl alcohol; at 180.0℃; for 1.0h;Microwave irradiation; B. Preparation of 4-methyl-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4yl)-piperidine-4-carboxylic acid. To a solution of 4-chloro-5-methyl-7H-pyrrolo[2,3-d]pyrimidine (0.274 g, 1.64 mmol) in isopropanol (10 mL) were added 4-methylpiperidine 4-carboxylic acid hydrochloric acid from step A (0.294 g, 1.64 mmol) and triethylamine (0.654 mL, 4.92 mmol). The reaction was heated to 180 C. for 1 hour under microwave conditions, concentrated, taken up with ice water, and neutralized to pH 3 with 6 N aq. HCl to precipitate the product. The product was collected by filtration and dried under vacuum overnight to give the title compound (0.42 g, 75%) as a gray solid. MS (ES+) [M+H]+=275.2.
  • 5
  • [ 919354-20-4 ]
  • [ 1388144-44-2 ]
  • [ 1388144-48-6 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In dimethyl sulfoxide; at 120.0℃;Inert atmosphere; Intermediate 32l -(5"formyl-2,3'-bipyridin-6'-yl)-4-methylpiperidine-4-carboxylic acid A mixture of 6.-fluoro-2,3'-bipyridine-5-carbaldehyde (Step A, Intermediate 28, 0.8 g, 3.96 mmol), 0.5 g, sodium bicarbonate (1.994 g, 23.74 mmol), <strong>[919354-20-4]4-methylpiperidine-4-carboxylic acid hydrochloride</strong> (1.422 g, 7.91 mmol) in DMSO (10 mL) was heated 120 C overnight under nitrogen. The mixture was then dried and. the residue was purified by MPLC (gredient to acetone) to afford product l-(5-fonnyl-2,3'-bipyridin-6'-yl)-4-methylpiperidine-4-carboxylic acid. LC-MS (ES, m/z) C18Hi9N303: 325; Found: 326 [M+H]+.
  • 6
  • [ 919354-20-4 ]
  • [ 1446358-48-0 ]
  • C24H22F2N6O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With triethylamine; In tetrahydrofuran; water; at 80.0℃; for 18.0h; General procedure: General procedure B A solution of amino nucleophile (3 equiv.), triethylamine (10 equiv.), and Intermediate 1 (1 equiv.) was stirred in dioxane and water (2:1 ratio) at 90 C until complete consumption of starting material was observed by LC/MS. The solution was diluted withiN hydrochloric acid and dichloromethane. The layers were then separated and thelayer was extracted with dichloromethane. The organics were combined, dried over magnesium sulfate, filtered, and the solvent was removed in vacuo. Purification yielded theproduct. The title compound was prepared following general procedure B, except 4-methylpiperidine-4-carboxylic acid (as the HC1 salt) was the amine reactant (1.1 equiv.), 4 equivalents of triethyl amine was used, and the contents were heated to 80 C for 18 h as a solution in THF/water (10:1). Contents extracted with ethyl acetate during workup. The crude material was purified via silica gel chromatography utilizing a 1-10% methanolldichloromethane gradient over 30 minutes to deliver the desired compound, Compound 1-124 as an off-white solid (36.1 mg, 95% yield).1H NMR (400 MHz, CDC13) oe (ppm): 8.49 (s, 1H), 8.16 - 8.28 (d, 1H), 7.35 -7.44 (m, 1H),7.17 - 7.26 (m, 1H), 6.95 - 7.10 (m, 2H), 6.87 (m, 1H), 6.62 (s, 1 H), 6.00 (s, 2H), 4.34 - 4.48 (m, 1H), 3.36 - 3.48 (m, 1H), 2.36 - 2.41 (m, 1H), 1.58 - 1.68 (m, 1H), 1.34 (s, 3H), 0.71 -0.81 (m, 4H).
 

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