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Structure of 20386-22-5

Chemical Structure| 20386-22-5

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Product Details of [ 20386-22-5 ]

CAS No. :20386-22-5
Formula : C4H9ClN2O
M.W : 136.58
SMILES Code : Cl[H].NN1CCCC1=O
MDL No. :MFCD09258892
InChI Key :NYPFNJOTVWTWAF-UHFFFAOYSA-N
Pubchem ID :21992845

Safety of [ 20386-22-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 20386-22-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 35.91
TPSA ?

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

46.33 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

-0.16
Log Po/w (WLOGP)?

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

-0.1
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.

0.03
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

-0.24
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.09

Water Solubility

Log S (ESOL):?

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

-0.59
Solubility 35.4 mg/ml ; 0.259 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.

-0.36
Solubility 59.9 mg/ml ; 0.438 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

0.22
Solubility 229.0 mg/ml ; 1.67 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

No
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.

-7.25 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

2.0
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

2.0 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)

1.09

Application In Synthesis of [ 20386-22-5 ]

* 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 [ 20386-22-5 ]

[ 20386-22-5 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 150401-96-0 ]
  • [ 20386-22-5 ]
  • 3-(6-methyl-pyridin-2-yl)-3-(2-oxo-pyrrolidin-1-ylimino)-propionic acidethyl ester [ No CAS ]
  • 2
  • 2-(6-bromoquinolin-4-yl)-1-(6-methylpyridin-2-yl)ethanone [ No CAS ]
  • [ 20386-22-5 ]
  • 1-[2-(6-bromo-quinolin-4-yl)-1-(6-methyl-pyridin-2-yl)-ethylideneamino]-pyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
69.7% With pyridine; at 20℃; for 10h; Stir a mixture OF 2- (6-BROMO-QUINOLIN-4-YL)-1- (6-METHYL-PYRIDIN-2-YL)-ETHANONE (38. 5 g, 113 mmol) and <strong>[20386-22-5]1-aminopyrrolidinone hydrochloride</strong> (20 g, 147 mmol) in 115 mL pyridine at ambient temperature for 10 hours. Add about 50 g 4 A UNACTIVATED sieves. Continue stirring an additional 13 h and add 10-15 g silica and filter the mixture through a 50 g silica plug. Elute the silica plug with 3 L ethyl acetate. Combine the filtrates and concentrate in vacuo. Collect the hydrazone precipitate by filtration and suction dry to yield 33.3 g (69.7%) of the desired subtitled intermediate as an off-white solid. MS ES+ = 423 (M+1).
  • 3
  • 2-(7-bromo-quinolin-4-yl)-1-(6-methyl-pyridin-2-yl)-ethanone [ No CAS ]
  • [ 20386-22-5 ]
  • 1-[2-(7-Bromoquinolin-4-yl)-1-(6-methylpyridin-2-yl)-ethylideneamino] pyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With pyridine; In ethanol; for 18h; The product of Preparation 4 (1.3 g, 1.47 mmol), the product of Preparation 1 (0. 315 g, 2.31 mmol) and pyridine (1.47 mL) are dissolved in ETOH (6 mL) and stirred for 18 h. The mixture is concentrated to dryness and the residue chromatographed on silica gel (90% EtOAc/Hexanes) to give the title compound, 1.2 g (75%), as a yellow foam. 'H NMR (CDC13) 8 8.80-8. 75 (m, 1H), 7.95-7. 85 (m, 2H), 7.70-7. 60 (m, 1H), 7.45-7. 20 (m, 4H), 4.90 (s, 2H), 3.10-3. 00 (m, 2H), 2.20-2. 15 (m, 2H), 1.48-1. 35 (m, 2H).
  • 4
  • [ 150401-96-0 ]
  • [ 20386-22-5 ]
  • [ 700871-81-4 ]
YieldReaction ConditionsOperation in experiment
With pyridine; at 20℃; for 20h; B. Preparation of 3-[6-Methyl-(pyridin-2-yl)]-3-(2-oxo-pyrrolidin-l-ylimino)-propionic acid ethyl ester; EPO <DP n="16"/> Add l-aminopyrrolidin-2-one hydrochloride (Zubek, A. Z. Chem. 1969, 9(2), 58; 99.4 g, 0.73 mol) to a 3 L flask equipped with mechanical stirrer and nitrogen inlet. Add 3-[6-methyl-(pyridin-2-yl)]-3-oxo-propionic acid ethyl ester (Preparation 1, Part A; 154 g, 0.66 mol), and pyridine (280 mL). Stir the reaction mixture at room temperature for 20 h. Dilute the mixture with water (200 mL) and extract with toluene (2 x 250 mL).Combine the organic layers, filter, and concentrate in vacuo to yield the subtitled product (201 g) as a dark oil. MS (ES) m/z = 290 (M+H).
With pyridine; at 20℃; for 20h; Add L-AMINOPYRROLIDIN-2-ONE hydrochloride (Zubek, A. Z Chem. 1969, 9 (2), 58; 99.4 g, 0.73 mol) to a 3L flask equipped with mechanical stirrer and nitrogen inlet. Add 3- (6-methyl-pyridin-2-yl)-3-oxo-propionic acid ethyl ester (Preparation 1, Part A; 154 g, 0.66 mol), then pyridine (280 mL). Stir the reaction mixture at room temperature for 20 h. Dilute the mixture with water (200 mL) and extract with toluene (2 x 250 mL). Combine the organic layers, filter, and concentrate in vacuo to yield the subtitled product (201 g) as a dark oil. MS ES+ m/e 290 (M+1).
In pyridine; at 20℃; for 20h; Add l-aminopyrrolidin-2-one hydrochloride (Zubek, A. Z Chem. 1969, 9 (2), 58 ; 99.4 g, 0.73 mol) to a 3 L flask equipped with mechanical stirrer and nitrogen inlet. Add 3- [6-methyl- (pyridin-2-yl)]-3-oxo-propionic acid ethyl ester (154 g, 0.66 mol), and pyridine (280 mL). Stir the reaction mixture at room temperature for 20 h. Dilute the mixture with water (200 mL) and extract with toluene (2 x 250 mL). Combine the organic layers, filter, and concentrate in vacuo to yield the subtitled product (201 g) as a dark oil. MS ES+ m/e 290 (M+1).
  • 5
  • [ 26510-52-1 ]
  • [ 20386-22-5 ]
  • 3-(2-Oxo-pyrrolidin-1-yl-imino)-3-pyridin-2-yl-propionic Acid Ethyl Ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% In pyridine; at 20℃; for 16h; Ethyl picolinoylacetate (4.7 g, 24.3 mmol) and the product of Preparation 1 (5.0 g, 36.5 mmol) are mixed in 10 ML of pyridine. The reaction mixture is stirred overnight at RT and then evaporated to a solid mass. The crude mixture is purified by MPLC on silica gel (40% EtOAc/Hexanes) to give the title compound, 6.63 g (95%), as a liquid. MS ES+ m/e 276. 1 (M+1).
  • 6
  • [ 26510-52-1 ]
  • [ 20386-22-5 ]
  • [ 700871-80-3 ]
YieldReaction ConditionsOperation in experiment
98% With pyridine; at 20℃; for 20h; B. Preparation of 3-(2-Oxo-pyrrolidin-l-ylimino)-3-(pyridin-2-yl)-propionic acid ethyl ester; Place l-aminopyrrolidin-2-one hydrochloride (Zubek, A. Z. Chem., 1969, 9(2), 58; 155.6 g, 1.14 mol) in a 3 L flask equipped with mechanical stirrer and nitrogen inlet. Add 3-oxo-3-pyridin-2-yl-propionic acid ethyl ester (Preparation 2, Part A; 200 g, 1.04 mol) and pyridine (400 mL). Stir the reaction mixture at room temperature for 20 h.Dilute the mixture with water (500 mL) and extract with toluene (2 x 500 mL). Combine EPO <DP n="19"/>the organic layers, dry (sodium sulfate), filter, and concentrate in vacuo to yield 280 g (98%) of the subtitled compound as a dark oil. MS (ES) m/z = 276 (M+H).
98% With pyridine; at 20℃; for 20h; Place L-AMINOPYRROLIDIN-2-ONE hydrochloride (Zubek, A. Z. CHEM., 1969, 9 (2), 58; 155.6 g, 1.14 mol) in a 3 L flask equipped with mechanical stirrer and nitrogen inlet. Add 3-oxo-3-pyridin-2-yl-propionic acid ethyl ester (200 g, 1.04 mol) then pyridine (400 mL). Stir the reaction mixture at room temperature for 20 h. Dilute the mixture with water (500 mL), and-extract with toluene (2 x 500 mL). Combine the organic layers, dry (sodium sulfate), filter and concentrate in vacuo to yield the subtitled compound as a dark oil (280 g, 98%). MS ES+ M/E 276 (M+1).
98% In pyridine; at 20℃; for 20h; Place l-aminopyrrolidin-2-one hydrochloride (Zubek, A. Z. Chem., 1969, 9 (2), 58 ; 155. 6 g, 1.14 mol) in a 3 L flask equipped with mechanical stirrer and nitrogen inlet. Add 3-oxo-3-pyridin-2-yl-propionic acid ethyl ester (Preparation 3-A ; 200 g, 1.04 mol) and pyridine (400 mL). Stir the reaction mixture at room temperature for 20 h. Dilute the mixture with water (500 mL) and extract with toluene (2 x 500 mL). Combine the organic layers, dry (sodium sulfate), filter, and concentrate in vacuo to yield 280 g (98%) of the subtitled compound as a dark oil. MS ES+ m/e 276 (M+1).
  • 7
  • [ 79289-48-8 ]
  • [ 20386-22-5 ]
YieldReaction ConditionsOperation in experiment
81% With hydrogenchloride; In water; for 1.5h;Heating / reflux; 4-Chlorobutyryl chloride (57 mL, 510 mmol) is added to a solution of benzophenone hydrazone (100 g, 510 mmol) and pyridine (41 mL, 510 mmol) in anhydrous CH2C12 (520 mL) under nitrogen at a rate that maintained a gentle reflux throughout the addition. The mixture is stirred for 0.5 h and poured into water (1 L). The layers are separated and the organic layer is washed with brine, dried (NA2S04), filtered, and concentrated in vacuo to yield 4-chloro-butyric acid benzhydrylidene-hydrazide as a residue. MS ES+ M/E 301. 1 (M+1). This residue is dissolved in THF (1.5 L), and the solution cooled in an ice-water bath, treated with portions of NaH (60% suspended in mineral oil, 20 g, 498 mmol) and stirred for 1 h. To the mixture is added saturated aqueous NH4CL solution (1 L) and EtOAc (1 L). The layers are separated and the organic solution washed with brine, dried (NA2SO4), filtered and concentrated in vacuo to yield 1- (BENZHYDRYLIDENEAMINO) pyrrolidin-2-one as a residue. 'H NMR (CDCl3) : 8 7.58-7. 62 (m, 2H), 7.39-7. 46 (m, 4H), 7.29-7. 36 (m, 4H) 3.31 (t, J = 7 Hz, 2H), 2.32 (t, J = 7 Hz, 2H), 1.91 (quintet, J = 7 Hz, 2H); MS ES+ M/E 265.1 (M+1). This residue is suspended in water (3 L), treated with concentrated HC1 solution (80 mL), and heated to reflux for 1.5 h. The reaction is cooled to RT and extracted twice with CH2CL2. The aqueous portion is concentrated in vacuo followed by azeotropic removal of water with three portions of absolute ethanol and three portions of toluene to yield the title compound, 56 g (81%), as a white solid. 'H NMR (DMSO-d6): 8 3.58 (t, J = 7 Hz, 2H), 2.33 (t, J = 7Hz, 2H), 2.04 (quintet, J = 7 Hz, 2H), TOF MS ES+ exact mass calculated for C4H8N2 (M+): M/Z = 100.0637. Found: 100.0641.
  • 8
  • [ 94-02-0 ]
  • [ 20386-22-5 ]
  • [ 660432-30-4 ]
YieldReaction ConditionsOperation in experiment
36% To a solution of [1-AMINO-PYRROLIDINE-2-ONE] hydrochloride (3.8 g, 27.8 mmol) (WO 02/094833) add ethylbenzoylacetate (4.3 mL, 25 mmol) followed by pyridine (10 mL) at room temperature under nitrogen. Stir the mixture at room temperature for 20 hours and then, dilute with water (50 mL) and extract with toluene (2 x 50 mL). Dry the combined organic layers [(MGS04)] and concentrate in vacuo to give a brown oil, 6.23 g, [82%] yield, and treat with NaOEt (freshly prepared, 3.1 g, 45.4 mmol, 2 equiv) in toluene at [120C] for 8 hours. Cool the mixture to room temperature and add water (100 mL) and concentrated HCl until a pH of 4 is reached. Extract the mixture with EtOAc (3 x 200 mL) and dry [(MGS04)] the combined organic layers and concentrate in vacuo. Purify the residue in a biotage system (eluent: [CH2C12/MEOH] 40: 1) to obtain a yellow solid, 1. [8] g, 36% yield. MS [(ES+)] : [NEZ] = 257.1 [(M+H) +]
  • 9
  • 2-(7-methoxyquinolin-4-yl)-1-pyridin-2-ylethanone [ No CAS ]
  • [ 20386-22-5 ]
  • 1-[2-(7-methoxyquinolin-4-yl)-1-pyridin-2-ylethylideneamino]pyrrolidin-2-one [ No CAS ]
  • 10
  • [ 476472-30-7 ]
  • [ 20386-22-5 ]
  • 1-(2-(8-fluoroquinolin-4-yl)-1-(6-methylpyridin-2-yl)ethylideneamino)pyrrolidin-2-one [ No CAS ]
  • 11
  • 2-(6-bromoquinolin-4-yl)-1-(6-methylpyridin-2-yl)ethanone [ No CAS ]
  • [ 20386-22-5 ]
  • 1-(2-(6-bromoquinolin-4-yl)-1-(6-methylpyridin-2-yl)ethylideneamino)pyrrolidin-2-one [ No CAS ]
  • 12
  • [ 476472-32-9 ]
  • [ 20386-22-5 ]
  • 1-(1-(6-methylpyridin-2-yl)-2-(6-(trifluoromethoxy)quinolin-4-yl)ethylideneamino)pyrrolidin-2-one [ No CAS ]
  • 13
  • [ 21375-88-2 ]
  • [ 20386-22-5 ]
  • [ 1264670-28-1 ]
 

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