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Chemical Structure| 1000796-62-2 Chemical Structure| 1000796-62-2

Structure of 1000796-62-2

Chemical Structure| 1000796-62-2

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Product Details of [ 1000796-62-2 ]

CAS No. :1000796-62-2
Formula : C10H21ClN2O2
M.W : 236.74
SMILES Code : O=C(N1CC(N)CCC1)OC(C)(C)C.[H]Cl
MDL No. :MFCD06691424
InChI Key :DUNAVVRRZJQGCZ-UHFFFAOYSA-N
Pubchem ID :17750334

Safety of [ 1000796-62-2 ]

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

Computational Chemistry of [ 1000796-62-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 0
Fraction Csp3 0.9
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 66.27
TPSA ?

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

55.56 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

1.53
Log Po/w (WLOGP)?

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

1.77
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.

1.15
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

0.32
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.95

Water Solubility

Log S (ESOL):?

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

-2.07
Solubility 2.0 mg/ml ; 0.00844 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.

-2.31
Solubility 1.17 mg/ml ; 0.00495 mol/l
Class?

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

-0.92
Solubility 28.5 mg/ml ; 0.12 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.

-6.66 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

0.0
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)

2.71

Application In Synthesis of [ 1000796-62-2 ]

* 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.

  • Downstream synthetic route of [ 1000796-62-2 ]

[ 1000796-62-2 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 1000796-62-2 ]
  • N-benzyldiethanolamine hydrochloride [ No CAS ]
  • tert-butyl 3-(4-benzylpiperazin-1-yl)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With sodium hydrogencarbonate; In ethanol; for 4h;Heating / reflux; tert-Butyl 3-(4-benzylpiperazin-1 -yl)piperidine-1 -carboxylate (XXIc); 4.90 g (21.1 mmol) of benzylbis(2-chloroethyl)amine hydrochloride were dissolved in ethanol (120 ml) and, while stirring, 5.0O g (21.1 mmol) of tert-butyl 3- aminopiperidine-1 -carboxylate hydrochloride and 14.2 g (169 mmol) of sodium bicarbonate were added. The resulting reaction solution was heated under reflux for 4 h. The cooled reaction mixture was concentrated in vacuo, 100 ml of water were added, and the aqueous phase was extracted with ethyl acetate (4x60 ml). The combined organic phases were washed with saturated aqueous NaHCO3 solution, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel (mobile phase gradient 0-5% methanol in dichloromethane). Yield: 6.99 g (75%) of yellow solid Yield: 5.82 g (77%) of yellow oil MS (API-ES,pos) m/z = 360 [M+H]+
  • 2
  • [ 186519-92-6 ]
  • [ 1000796-62-2 ]
  • [ 1034769-83-9 ]
YieldReaction ConditionsOperation in experiment
29% Svnthesis 8-1 -B; f-Butyl 3-(4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamido)piperidine-1-carboxylate; A solution of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid (18 mg, 0.09 mmol), HATU (45 mg, 0.12 mmol), and diisopropylethylamine (80 mul_, 0.46 mmol) in DMF (1 mL) was stirred at room temperature for 30 minutes. ferf-Butyl 3-aminopiperidine-1- carboxylate hydrochloride (28 mg, 0.12 mmol) in DMF (0.5 mL) was added and the resulting solution was stirred for 16 hours. The mixture was diluted with brine and extracted with ethyl acetate. The combined organic layers were washed sequentially with NaHCO3 solution, citric acid, and brine, then dried (Na2SO4), filtered, and concentrated. Purification by preparative TLC, eluting with ethyl acetate, gave the title compound as a light yellow oil (10 mg, 29%).1H NMR (500 MHz, CD3OD) delta 1.47 (9H, s), 1.49-1.69 (2H, m), 1.71-1.84 (1 H, m), 2.02- 2.11 (1 H, m), 3.13-3.27 (1 H, m), 3.54-3.68 (1 H, m), 3.86-3.96 (2H, m), 4.00-4.09 (1 H, m), 7.92 (1 H, s), 8.61 (1 H, s); LC-MS Rt 4.29 min; m/z (ESI) 380 [MH+].
  • 3
  • [ 1000796-62-2 ]
  • tert-butyl 3-aminopiperidine-1-carboxylate [ No CAS ]
  • 4
  • [ 33252-28-7 ]
  • [ 1000796-62-2 ]
  • [ 1062196-26-2 ]
YieldReaction ConditionsOperation in experiment
56% With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 140.0℃; for 0.75h;Microwave irradiation; Example 67A; tert-Butyl 3-[(5-cyanopyridin-2-yl)amino]piperidine-1-carboxylate In analogy to the preparation of Example 60A, 85 mg (56% of theory) of the product are obtained as a solid from 100 mg (0.49 mmol) of <strong>[1000796-62-2]tert-butyl 3-aminopiperidine-1-carboxylate hydrochloride</strong> and 138 mg (0.99 mmol) of 6-chloropyridine-3-carbonitrile.LCMS (method 6): Rt=1.81 min. (m/z=303 (M+H)+)1H-NMR (400 MHz, DMSO-d6): delta=8.40 (d, 1H), 7.68 (d, 1H), 7.53 (d, 1H), 6.59 (d, 1H), 4.12 (s, br, 3H), 3.80 (s, br, 1H), 3.1-3.7 (m, 2H), 1.90 (m, 1H), 1.74 (m, 1H), 1.3-1.6 (m, 1H), 1.27 (s, 9H).
YieldReaction ConditionsOperation in experiment
99% Step B tert-butyl 3-aminopiperidine-1-carboxylate hydrochloride Using the compound (2.04 g, 6.17 mmol) obtained in step A and according to the method of Reference Example 9, step C, the title compound (1.45 g, yield 99%) was obtained as a colorless solid. 1H-NMR (300 MHz, DMSO-d6); delta(ppm) 1.3-1.6 (m, 2H), 1.43 (s, 9H), 1.6-1.8 (m, 1H), 1.9-2.0 (m, 1H), 2.7-3.1 (m, 3H), 3.6-3.8 (m, 1H), 3.9-4.0 (m, 1H), 8.23 (brs, 3H).
  • 6
  • [ 1000796-62-2 ]
  • [ 1694-92-4 ]
  • tert‐butyl 3‐(2‐nitrobenzenesulfonamido)piperidine‐1‐carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20.0℃; for 16h; 2- Nitrobenzenesulfonyl chloride (200 mg; 0.90 mmol; 1 eq.), 3- aminopiperidine-1-carboxylic acid tert-butyl ester hydrochloride (320 mg; 1.35 mmol; 1.5 eq.), DIPEA (0.47 mL; 2.71 mmol; 3 eq.), THF anhydrous (10 mL) are stirred at room temperature for 16 h. The reaction mixture is evaporated under reduced pressure, dissolved in EtOAc (50 mL), washed with water (3 x 20 mL) and brine (2 x 10 mL). The organic layer is dried over Na2S04, filtered, and evaporated to dryness. The crude tert-butyl 3- (2-nitrobenzenesulfonamido)piperidine-1-carboxylate (354 mg; 0.90 mmol; 99%; yellow oil; UPLC purity: 98%) is used in the next step without further purification.
99% With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20.0℃; for 16h;Inert atmosphere; A mixture of2-nitrobenzenesulfonyl chloride4(200 mg; 0.90 mmol; 1 eq.),<strong>[1000796-62-2]tert-butyl 3-aminopiperidine-1-carboxylate hydrochloride</strong> (320 mg; 1.35 mmol; 1.5 eq.), DIPEA (0.47 mL; 2.71 mmol; 3 eq.) in anhydrous THF (10 mL) was stirred at room temperature for 16 h under argon. The reaction mixture was concentratedin vacuo, dissolved in EtOAc (50 mL) and the resulting solution was washed with water, 1 M aq. HCl, sat. aq. NaHCO3and brine. The organic layer was dried over Na2SO4, filtered, and evaporated to dryness. The crudetert-butyl 3-(2-nitrobenzenesulfonamido)piperidine-1-carboxylate (354 mg; 0.90 mmol; yield: 99%; yellow oil; UPLC purity: 98%) was used in the next step without further purification.m/z[M+H]+: 386.05.
 

Historical Records

Technical Information

Categories

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