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Chemical Structure| 26116-13-2 Chemical Structure| 26116-13-2

Structure of 26116-13-2

Chemical Structure| 26116-13-2

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Product Details of [ 26116-13-2 ]

CAS No. :26116-13-2
Formula : C8H16N2
M.W : 140.23
SMILES Code : NCC1N(CC=C)CCC1
MDL No. :MFCD01317559
InChI Key :HTGKTSVPJJNEMQ-UHFFFAOYSA-N
Pubchem ID :117296

Safety of [ 26116-13-2 ]

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

Computational Chemistry of [ 26116-13-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 47.5
TPSA ?

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

29.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.15
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

0.52
Log Po/w (WLOGP)?

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

0.21
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.

0.76
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

0.89
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.91

Water Solubility

Log S (ESOL):?

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

-0.84
Solubility 20.3 mg/ml ; 0.145 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.

-0.71
Solubility 27.6 mg/ml ; 0.197 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

-0.96
Solubility 15.2 mg/ml ; 0.109 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.

-6.79 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)

2.01

Application In Synthesis of [ 26116-13-2 ]

* 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 [ 26116-13-2 ]

[ 26116-13-2 ] Synthesis Path-Downstream   1~11

  • 2
  • [ 64269-79-0 ]
  • 2,3-dimethoxy-5-sulphamoyl benzoic acid [ No CAS ]
  • [ 26116-13-2 ]
  • [ 66644-81-3 ]
YieldReaction ConditionsOperation in experiment
60% In tetrahydrofuran; water; EXAMPLE 1 N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide 7.8 g (0.03 mole) of 2,3-dimethoxy-5-sulphamoylbenzoic acid, 200 ml of tetrahydrofuran and 7.3 g (0.045 mole) of carbonyl-diimidazole were placed in a 500-ml flask fitted with an agitator, a thermometer and a condenser. The mixture was agitated for 30 minutes at normal temperature after which 6.7 g (0.048 mole) of 1-allyl-2-aminomethylpyrrolidine was added. The mixture was left under agitation for 5 hours at 20 C. and then the solvent was evaporated under vacuum and the residue treated with 150 ml of water. The crystals were washed and dried. 6.9 g of N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide was obtained. (Yield: 60%; melting point: 113-114 C.)
  • 3
  • 2,3-dimethoxy-5-sulphamoyl benzoic acid [ No CAS ]
  • [ 26116-13-2 ]
  • [ 66644-81-3 ]
YieldReaction ConditionsOperation in experiment
61% With triethylamine; In 2-ethyl-5-phenylisoxazolium-3'-sulphonate; ethyl acetate; acetonitrile; EXAMPLE 2 N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide A 250-ml flask was used, fitted with an agitator, a thermometer and a bromine funnel. In this flask were placed 10.15 g (0.04 mole) of N-ethyl-5-phenyl-isoxazolium-3'-sulphonate, 100 ml of acetonitrile and, in small quantities at 0 C., a mixture of 10.4 g (0.04 mole) of 2,3-dimethoxy-5-sulphamoylbenzoic acid, 4.1 g (0.04 mole) of triethylamine and 80 ml of acetonitrile. The mixture was left for one hour at 0 C. and then for two hours at ambient temperature. 11.2 g (0.08 mole) of 1-allyl-2-amino-methylpyrrolidine was added drop by drop at 20 C. and the mixture was kept under agitation at ambient temperature for three hours. The crystals formed were filtered, washed with water and dried in an oven at 50 C. After crystallation in ethyl acetate 9.3 g of N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide was obtained. (Yield: 61%; melting point: 117-118
  • 4
  • 2,3-dimethoxy-5-sulfonamidobenzoic acid methyl ester [ No CAS ]
  • [ 26116-13-2 ]
  • [ 66644-81-3 ]
YieldReaction ConditionsOperation in experiment
68% In hydrogenchloride; water; ethylene glycol; EXAMPLE 8 Dextrorotatory N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide 135 g of methyl-2,3-dimethoxy-5-sulphamoylbenzoate and 670 ml of ethylene glycol were placed in a 2-liter flask. Dissolution was obtained at about 85 C. and then the mixture was cooled to about 55 C. 82.5 g of dextrorotary 1-allyl-2-aminomethylpyrrolidine was added and the reaction mixture heated to 50 C. until a test sample was totally soluble in dilute hydrochloric acid. When the reaction was complete 3.5 liters of water was added and the mixture extracted with methylene chloride. When the solvent had evaporated the solid formed was drained, washed with water, recrystallized from absolute alcohol and dried at 40 C. 128 g of dextrorotatory N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide was obtained. (Yield: 68%; melting point: 144-145 C.) (alpha) D20 =+63 (solution at 5% in dimethyl-formamide).
66% In hydrogenchloride; water; ethylene glycol; EXAMPLE 3 N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide 55 g (0.2 mole) of methyl 2,3-dimethoxy-5-sulphamoylbenzoate and 275 ml of glycol were poured into a 500 ml flask fitted with an agitator and a thermometer. Dissolution was obtained at about 85 C. after which the mixture was cooled to 50 C. 35 g of 1-allyl-2-aminomethylpyrrolidine was added and the reaction mixture was heated to 50 C. until a test sample was totally soluble in dilute hydrochloric acid. When the reaction was complete 1 liter of water was added and the mixture was extracted with methylene chloride. When the solvent had evaporated the solid obtained was drained, washed with water and re-crystallized in 50% alcohol. 50.5 g of N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide was obtained. (Yield: 66%; melting point: 108-110 C.).
54% In hydrogenchloride; water; ethylene glycol; EXAMPLE 9 Laevorotatory N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide 135 g of methyl-2,3-dimethoxy-5-sulphamoylbenzoate and 675 ml of ethylene glycol were placed in a 2-liter flask. Dissolution was obtained at about 85 C. and then the mixture was cooled to about 55 C. 83 g of laevorotatory 1-allyl-2-aminomethylpyrrolidine was added, and the reaction mixture was heated to 50 C. until a test sample was totally soluble in dilute hydrochloric acid. When the reaction was completed 3.5 liters of water was added and the mixture was extracted with methylene chloride. When the solvent had evaporated the solid formed was drained, washed with water, recrystallized from absolute alcohol and dried at 40 C. 120 g of laevorotatory N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide was obtained. (Yield: 54%; melting point: 144-145 C.) [alpha]D20 =-628 (solution at 5% in dimethyl-formamide).
  • 5
  • [ 57734-47-1 ]
  • [ 26116-13-2 ]
  • [ 66644-83-5 ]
YieldReaction ConditionsOperation in experiment
75% In ethanol; acetone; EXAMPLE 4 N-oxide of N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide 200 ml of acetone and 28 g of 1-allyl-2-aminomethylpyrrolidine were placed in a 500-ml flask fitted with a thermometer and an agitator. 50 g of 2,3-dimethoxy-5-sulphamoylbenzoyl chloride was stirred into the flask while the temperature was kept between 10 and 15 C. Agitation of the mixture was continued for one hour at +10 C. and then 10 ml of ethanolic hydrochloric acid (30g/100 ml) was added. When agitation had stopped the acetone was decanted and 100 ml of absolute ethanol added. After the mixture had been left to stand for one hour, the crystals obtained were filtered, washed with 20 ml of absolute ethanol and then dried at 50 C. 56.3 g of N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide hydrochloride was obtained. (Yield: 75%).
  • 6
  • [ 21550-48-1 ]
  • [ 26116-13-2 ]
  • [ 54929-62-3 ]
YieldReaction ConditionsOperation in experiment
6. 2-(6-amino nicotinamidomethyl)-1-allyl pyrrolidine, M.P. 106-107C (ethyl acetate), starting from 6-acetamido nicotinic acid and 2-aminomethyl-1-allyl pyrrolidine.
  • 7
  • [ 3167-49-5 ]
  • P Cl3 [ No CAS ]
  • [ 26116-13-2 ]
  • [ 54929-62-3 ]
YieldReaction ConditionsOperation in experiment
30. 2-(6-amino nicotinamidomethyl)-1-allyl pyrrolidine, M.P. 106-107C (ethyl acetate), starting from P Cl3, 2-aminomethyl-1-allyl pyrrolidine and 6-amino nicotinic acid.
  • 8
  • [ 66410-38-6 ]
  • [ 26116-13-2 ]
  • N-(1-allyl-2-pyrrolidylmethyl)-7-methylsulfamoyl-1,4-benzodioxane-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
68.7% With sulfuric acid; ammonia; In chloroform; water; N-(1-allyl-2-pyrrolidylmethyl)-7-methylsulfamoyl-1,4-benzodioxane-5-carboxamide 69 g of <strong>[26116-13-2]1-allyl-2-aminomethyl-pyrrolidine</strong> and 432 ml of chloroform were introduced into a 1-liter balloon flask provided with a thermometer and an agitator. 144 g of 7-methylsulfamoyl-1,4-benzodioxane-5-carbonyl chloride were added in portions with the temperature being maintained at 5-10 C. Agitation of the mixture was continued for one hour and then the mixture was treated with 1,750 ml of water. After distillation of the chloroform the mixture was acidified to a pH value of 4 with 4 ml of 20% sulfuric acid and then filtered on carbon black. The solution of the sulfate formed was rendered alkaline with 60 ml of 20% ammonia. After crystallization, the base was dried off, washed with water and dried at 40 C. After recrystallization with acetonitrile 134 g of N-(1-allyl-2-pyrrolidylmethyl)-7-methyl-sulfamoyl-1,4-benzodioxane-5-carboxamide was produced (M.P.: 142-143 C.; yield: 68.7%). The nuclear magnetic resonance spectra were found to be compatible with the proposed structure.
  • 9
  • [ 66410-46-6 ]
  • [ 26116-13-2 ]
  • N-(1-allyl-2-pyrrolidylmethyl)-7-ethylsulfonyl-1,4-benzodioxane-5-carboxamide hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In chloroform; EXAMPLE 14 N-(1-allyl-2-pyrrolidylmethyl)-7-ethylsulfonyl-1,4-benzodioxane-5-carboxamide hydrochloride 58 g of <strong>[26116-13-2]1-allyl-2-aminomethyl-pyrrolidine</strong> and 360 ml of chloroform were introduced into a balloon flask provided with an agitator and a thermometer and then, with the temperature being maintained at 5-10 C., 120 g of 7-ethylsulfonyl-1,4-benzodioxane-5-carbonyl chloride was added. After agitation of the mixture and the addition of a liter of water, the chloroform was distilled. The resulting solution was filtered on carbon black and then the base was precipitated by the addition of 40 ml of 30% soda lye. The resulting crystals were dried off, washed with water and then dried. 152 g of N-(1-allyl-2-pyrrolidylmethyl)-7-ethylsulfonyl-1,4-benzodioxane-5-carboxamide was produced (M.P.: 78-80 C.; yield: 93.4%). 146 g of the resulting base was dissolved hot in 290 ml of absolute alcohol, and then the solution was filtered on carbon black and acidified by the addition of a solution of 13.5 g of hydrochloric acid in 100 ml of absolute alcohol. After cooling the crystals formed were dried off, washed with absolute alcohol and dried and then purified by recrystallization from absolute alcohol. 119.5 g of N-(1-allyl-2-pyrrolidylmethyl)-7-ethylsulfonyl-1,4-benzodioxane-5-carboxamide hydrochloride was produced (M.P.: 138-140 C.; yield: 75%).
  • 10
  • [ 26116-13-2 ]
  • 2-(18)F-fluoro-2-deoxy-D-glucose [ No CAS ]
  • [ 1563187-72-3 ]
YieldReaction ConditionsOperation in experiment
With sodium acetate; aniline; sodium chloride; In water; 18F-FDG<strong>[26116-13-2]NAP</strong>: To synthesize 18F-FDG<strong>[26116-13-2]NAP</strong> (15), 9 muL aniline catalyst and 5 muL <strong>[26116-13-2]NAP</strong> (13) was dissolved in 0.1 mL acetate buffer and 0.1 ml: of 1 mCi 18F-FDG (8, in 0.9% sterile saline) was added to this mixture. The reaction was monitored by radioTLC at 0.17, 1, 2, 3, 4 hours using the Optiquant software and product was confirmed by coelution of reference standard.
  • 11
  • [ 7226-39-3 ]
  • [ 26116-13-2 ]
  • [ 1563187-69-8 ]
YieldReaction ConditionsOperation in experiment
With sodium acetate; acetic acid; aniline; In water; at 20.0℃; for 4.0h;pH 4.2; FDG<strong>[26116-13-2]NAP</strong>: To synthesize FDG<strong>[26116-13-2]NAP</strong>, 7 mul (5.50×10-5 mole) of <strong>[26116-13-2]NAP</strong> and 5.0 mg (2.75×10-5 mole) FDG were dissolved in 0.2 mL acetate buffer (0.1M sodium acetate-acetic acid, pH4.2) and 5 mul aniline as a catalyst. The solution was left at room temperature for 4 hrs. Preparatory TLC was performed using 9:1 dichloromethane-methanol to provide FDG<strong>[26116-13-2]NAP</strong> in 31% yield MS: m/z 305 [M+H]+. Aniline used as a catalyst also showed small amounts (approx. 20-30%) of the FDG adduct (MS: m/z 280 [M+Na]+.
 

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