Structure of 76114-73-3
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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. : | 76114-73-3 |
Formula : | C8H13NO2 |
M.W : | 155.19 |
SMILES Code : | O=C(OCC#C)NCCCC |
MDL No. : | MFCD06411065 |
InChI Key : | JTDBXHIIVZZXDH-UHFFFAOYSA-N |
Pubchem ID : | 10877354 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H317-H412 |
Precautionary Statements: | P273-P280 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.62 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.21 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.33 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.5 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.31 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.23 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.38 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.05 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.49 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.23 |
Solubility | 9.11 mg/ml ; 0.0587 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.72 |
Solubility | 2.99 mg/ml ; 0.0193 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.7 |
Solubility | 3.13 mg/ml ; 0.0202 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 |
Yes |
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 |
-6.32 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) |
2.28 |
* 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 |
---|---|---|
93.2 - 93.5% | EXAMPLE I; A reactor was charged with 330g of water which was then cooled to a temperature of 0-8C. To the cooled water, while stirring was added 3.4 grams of a nonionic surfactant agent MERPOL HCS and 16. 85g of butyl PROPYNYL carbamate while maintaining the temperature between 0-8 C. The reactor was further charged with 8.85g of a 50% aqueous solution of sodium hydroxide and 16.28 grams of sodium iodide which had been previously dissolved in 50g of water. The temperature was maintained between 5-8C. The reactor with strong agitation was slowly charged with 70.2g of a 13.6% solution of sodium hypochlorite while maintaining the reaction mass at a temperature of between 6 and 11 C. The temperature was allowed to ramp up slightly to 15-20C and the reaction mass was agitated for 90 minutes. The reaction mass was then slowly heated to a temperature of 35-40 C. The ramping up of the temperature was effected at a rate of 0.25 to 0. 75C per minute. With agitation the pH of the reaction mass was then adjusted to 6.9 with acetic acid. The pH reaction mass was then adjusted to 6.6 with sodium bisulfite. The temperature was then ramped up to 55 to 59C at a rate of. 25 to. 75C per minute. When a temperature reached a range of 55-59C cooling was applied to the reaction mass to ramp the temperature of the reaction mass down to 25-30 C, at a ramp down rate of 0.33-0. 75C per minute. The reaction mass was then agitated for 10 minutes and then the reaction mass was filtered. The filtration cake was washed twice with 100 mi of water. The cake was then dried at 35 C to a constant weight. The reaction achieved a yield of 93.5% of IPBC which assayed at 98.7% IPBC; EXAMPLE 3; A reactor was charged with 1400 gal of water which was then cooled to a temperature of 0-8 C. To the cooled water, while stirring was added to 87 pounds of a nonionic surfactant agent Merpol HCS and 429 pounds of <strong>[76114-73-3]butyl propynyl carbamate</strong> while maintaining the temperature between 0-8 C. The reactor was further charged with 214 pounds of a 50% aqueous solution of sodium hydroxide and 853 pounds of 50% sodium iodide solution. The temperature was maintained between 5-8 C. The reactor with strong agitation was slowly charged with 1780 pounds of a 13.6% solution of sodium of sodium hypochlorite while maintaining the reaction mass at a temperature of between 6 and 11C. The temperature was allowed to ramp up slightly to 15-20C and the reaction mass was agitated for 90 minutes. The reaction mass was then slowly heated to a temperature of 35-40C. The ramping up of the temperature was effected at a rate of 0.25 to 0. 75 C per minute. With agitation the pH of the reaction mass was then adjusted to 6.9 with acetic acid. The pH reaction mass was then adjusted to 6.6 with sodium bisulfite. The temperature was then tamped up to 55 to 59C at a rate of 0.25 to 0. 75C per minute. With agitation the pH of the reaction mass was then adjusted to 6.9 with acetic acid. The pH reaction mass was then adjusted to 6.6 with sodium bisulfite. The temperature was then ramped up to 55 to 59C at a rate of 0.25 to 0. 75C per minute. When a temperature reached a range of 55-59C, cooling was applied to the reaction mass to ramp the temperature of the reaction mass down to 25-30C, at a ramp down rate of 33-75C per minute. When a temperature reached a range of 55-59C, cooling was applied to the reaction mass to ramp the temperature of the reaction mass down to 25-30C, at a ramp down rate of 33-75C per minute. The reaction mass was then agitated and then the reaction mass was centrifuged with water for 10 minutes. The cake was washed. The cake was then dried at 30-45C to a constant weight. The reaction achieved a yield of 93.2% of IPBC which assayed at 98.7% IPBC | |
93.5% | EXAMPLE 2; [0058] The reaction procedure of Example 1 was repeated except that in the iodination step potassium iodide was substituted for sodium iodine. The procedure produced IPBC at a yield of 93.5% wherein the resulting IPBC assayed at 98.7%. | |
93.2 - 93.5% | EXAMPLE 1; [0050] A reactor was charged with 330 g of water which was then cooled to a temperature of 0-8 C. [0051] To the cooled water, while stirring was added 3.4 grams of a nonionic surfactant agent Merpol HCS and 16.85 g of <strong>[76114-73-3]butyl propynyl carbamate</strong> while maintaining the temperature between 0-8 C. [0052] The reactor was further charged with 8.85 g of a 50% aqueous solution of sodium hydroxide and 16.28 grams of sodium iodide which had been previously dissolved in 50 g of water. The temperature was maintained between 5-8 C. [0053] The reactor with strong agitation was slowly charged with 70.2 g of a 13.6% solution of sodium hypochlorite while maintaining the reaction mass at a temperature of between 6 and 11 C. [0054] The temperature was allowed to ramp up slightly to 15-20 C. and the reaction mass was agitated for 90 minutes. The reaction mass was then slowly heated to a temperature of 35-40 C. The ramping up of the temperature was effected at a rate of 0.25 to 0.75 C. per minute. [0055] With agitation the pH of the reaction mass was then adjusted to 6.9 with acetic acid. The pH reaction mass was then adjusted to 6.6 with sodium bisulfite. The temperature was then ramped up to 55 to 59 C. at a rate of 0.25 to 0.75 C. per minute. [0056] When a temperature reached a range of 55-59 C. cooling was applied to the reaction mass to ramp the temperature of the reaction mass down to 25-30 C., at a ramp down rate of 0.33-0.75 C. per minute. [0057] The reaction mass was then agitated for 10 minutes and then the reaction mass was filtered. The filtration cake was washed twice with 100 ml of water. The cake was then dried at 35 C. to a constant weight. The reaction achieved a yield of 93.5% of IPBC which assayed at 98.7% IPBC.; A reactor was charged with 1400 gal of water which was then cooled to a temperature of 0-8 C. [0060] To the cooled water, while stirring was added to 87 pounds of a nonionic surfactant agent Merpol HCS and 429 pounds of <strong>[76114-73-3]butyl propynyl carbamate</strong> while maintaining the temperature between 0-8 C. [0061] The reactor was further charged with 214 pounds of a 50% aqueous solution of sodium hydroxide and 853 pounds of 50% sodium iodide solution. The temperature was maintained between 5-8 C. [0062] The reactor with strong agitation was slowly charged with 1780 pounds of a 13.6% solution of sodium of sodium hypochlorite while maintaining the reaction mass at a temperature of between 6 and 11 C. [0063] The temperature was allowed to ramp up slightly to 15-20 C. and the reaction mass was agitated for 90 minutes. The reaction mass was then slowly heated to a temperature of 35-40 C. The ramping up of the temperature was effected at a rate of 0.25 to 0.75 C. per minute. [0064] With agitation the pH of the reaction mass was then adjusted to 6.9 with acetic acid. The pH reaction mass was then adjusted to 6.6 with sodium bisulfite. The temperature was then tamped up to 55 to 59 C. at a rate of 0.25 to 0.75 C. per minute. [0065] With agitation the pH of the reaction mass was then adjusted to 6.9 with acetic acid. The pH reaction mass was then adjusted to 6.6 with sodium bisulfite. The temperature was then ramped up to 55 to 59 C. at a rate of 0.25 to 0.75 C. per minute. [0066] When a temperature reached a range of 55-59 C., cooling was applied to the reaction mass to ramp the temperature of the reaction mass down to 25-30 C., at a ramp down rate of 33-75 C. per minute. [0067] When a temperature reached a range of 55-59 C., cooling was applied to the reaction mass to ramp the temperature of the reaction mass down to 25-30 C., at a ramp down rate of 33-75 C. per minute. [0068] The reaction mass was then agitated and then the reaction mass was centrifuged with water for 10 minutes. The cake was washed. The cake was then dried at 30-45 C. to a constant weight. The reaction achieved a yield of 93.2% of IPBC which assayed at 98.7% IPBC. |
83% | With chlorine; sodium iodide; sodium hydroxide; In C12-C16-alcohol ethoxylate;Product distribution / selectivity; | Example 1At 5 C., 4.5 g of C12-C16-alcohol ethoxylate, 16.9 g of <strong>[76114-73-3]propargyl butylcarbamate</strong> (0.107 mol), 40.7 g of NaI solution (40% strength, 0.108 mol) and 25.8 g of NaOH solution (50% strength, 0.322 mol) are introduced as initial charge in 330 g of water. Chlorine (10.3 g, 0.145 mol) is then slowly introduced into the reaction mixture such that the temperature remains below 5 C. When the introduction is complete, the mixture is slowly heated to 20 C. and stirred at this temperature for 4 h. The precipitated solid is then isolated by filtration, washed with water and dried in vacuo.This gives 26.1 g of 3-iodo-2-propynyl N-10 butylcarbamate (purity: 95.4% (HPLC), polyiodized compounds: <0.1% (HPLC), yield:83%). |
With sodium hydroxide; sodium chloride; Iodine monochloride; In methanol; | EXAMPLE 1 A reactor (having a capacity of 200 ml and fitted with a condenser and a stirrer) was charged with 7.75 g (0.050 mole) of <strong>[76114-73-3]prop-1-yn-3-yl N-n-butylcarbamate</strong> and 80 g of methanol, followed by the addition of 8.3 g (equivalent to 0.073 mole) of a 35% aqueous solution of sodium hydroxide. While this solution was cooled to and maintained at 10 C., 30.5 g of a 15% aqueous solution of sodium chloride containing 28% iodine monochloride (equivalent to 0.053 mole) was added thereto over a period of 20 minutes. Furthermore, the solution was reacted at 15 C. for 2 hours. Thereafter, the reacted solution was neutralized with hydrochloric acid and extracted with 40 g of toluene. The reacted solution was further extracted five times with toluene and the combined toluene extract was dried over anhydrous magnesium sulfate. Finally, the toluene was removed by evaporation under reduced pressure to obtain 13.8 g of 1-iodo<strong>[76114-73-3]prop-1-yn-3-yl N-n-butylcarbamate</strong>. This product had a melting point of 65-67 C., its yield was 98.3 mole %, and no impurity was detected by its purity analysis. | |
With sodium hydroxide; sodium hypochlorite; iodine; In methanol; | COMPARATIVE EXAMPLE 4 A reactor (having a capacity of 200 ml and fitted with a condenser and a stirrer) was charged with 7.75 g (0.050 mole) of <strong>[76114-73-3]prop-1-yn-3-yl N-n-butylcarbamate</strong> and 80 g of methanol, followed by the addition of 8.3 g (equivalent to 0.073 mole) of a 35% aqueous solution of sodium hydroxide. While this solution was cooled to and maintained at 10 C., 6.73 g (equivalent to 0.027 mole) of iodine was added thereto. After 20.5 g of a 6% aqueous solution of sodium hypochlorite was subsequently added thereto, the solution was reacted for 2 hours while its temperature was maintained at 10 C. Thereafter, the reacted solution was neutralized with hydrochloric acid and extracted with 40 g of toluene. The reacted solution was further extracted five times with toluene and the combined toluene extract was dried over anhydrous magnesium sulfate. Finally, the toluene was removed by evaporation under reduced pressure to obtain 11.4 g of 1-iodo<strong>[76114-73-3]prop-1-yn-3-yl N-n-butylcarbamate</strong>. Its yield was 81.2 mole %, and its purity analysis revealed the presence of 0.5% of polyiodinated products (impurities). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With tetrabutylammomium bromide; In acetonitrile; | EXAMPLE I Synthesis of N-Butyl Propargyl Carbamate: A mixture of n-butyl bromide (8.8 g, 0.064 mole), propargyl alcohol (3 g, 0.054 mole), potassium cyanide (6.5 g, 0.08 mole) and tetrabutylammonium bromide (1.7 g, 0.005 mole) in acetonitrile (45 mL) was heated at 70C. under nitrogen for 22 hours. The insoluble precipitate was filtered off and the filtrate was concentrated on a rotary evaporator to give a yellow oil (6.7 g). Column chromatography (silica gel, 15/85 of ethyl acetate/hexane) gave a colourless oil (4.4 g, 53 %) of N-butyl propargyl carbamate. NMR (CDC13, ppm): 4.75 (2H, s), 3.2 (2H, m), 2.5 (1H, s), 1.4 (4H, m), 1.0 (3H, t).; GC/MS (m/e): 155 (M+), 112 (100 %), 74, 57, 56. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With copper(l) iodide; sodium hydroxide; In methanol; at 20℃; for 24.0h; | Typical procedure. A solution of the appropriate azide (2 mmol) in MeOH (3.0 mL) was added to a stirred mixture of the corresponding alkyne (2.1 mmol), a 0.5 N solution of NaOH (0.5 mL, 0.25 mmol) and CuI (0.019g, 0.1 mmol) in MeOH (2.0 mL). The reaction mixture was stirred at room temperature for 24h. The reaction mixture was filtered through celite, and the solvent was removed in vacuo. The final product was purified by column chromatography (SiO2, hexane/AcOEt 8:2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With C19H18N6O*Cu(1+)*I(1-); In dichloromethane; at 20℃; for 24.0h; | General procedure: The copper complex 4 (0.0268 g, 0.025mmol) was added to a stirred solution containing the corresponding alkyne (1.0mmol) and the appropriate azide (1.05mmol) in CH2Cl2 (10 mL). The resulting reaction mixture was stirred at room temperature for 24 h. The mixture was filtered through celite-activated charcoal. The solvent was removedunder reduced pressure and the final product was purified by crystallization. |
43% | With copper(l) iodide; sodium hydroxide; In methanol; at 20℃; for 24.0h; | Typical procedure. A solution of the appropriate azide (2 mmol) in MeOH (3.0 mL) was added to a stirred mixture of the corresponding alkyne (2.1 mmol), a 0.5 N solution of NaOH (0.5 mL, 0.25 mmol) and CuI (0.019g, 0.1 mmol) in MeOH (2.0 mL). The reaction mixture was stirred at room temperature for 24h. The reaction mixture was filtered through celite, and the solvent was removed in vacuo. The final product was purified by column chromatography (SiO2, hexane/AcOEt 8:2). |