Structure of 26116-13-2
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
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 |
29.26 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.15 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.52 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.21 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.76 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.89 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.84 |
Solubility | 20.3 mg/ml ; 0.145 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.71 |
Solubility | 27.6 mg/ml ; 0.197 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.96 |
Solubility | 15.2 mg/ml ; 0.109 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.79 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.01 |
* 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.
Yield | Reaction Conditions | Operation 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.) |
Yield | Reaction Conditions | Operation 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 |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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%). |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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%). |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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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