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Structure of 2935-90-2
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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. : | 2935-90-2 |
Formula : | C4H8O2S |
M.W : | 120.17 |
SMILES Code : | O=C(OC)CCS |
MDL No. : | MFCD00004895 |
InChI Key : | LDTLDBDUBGAEDT-UHFFFAOYSA-N |
Pubchem ID : | 18050 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H227-H301+H331-H312-H410 |
Precautionary Statements: | P210-P261-P264-P270-P271-P273-P280-P301+P310+P330-P302+P352+P312-P304+P340+P311-P370+P378-P391-P403+P233-P403+P235-P405-P501 |
Class: | 6.1 |
UN#: | 2810 |
Packing Group: | Ⅲ |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.75 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 30.56 |
TPSA ? Topological Polar Surface Area: Calculated from |
65.1 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.61 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.34 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.48 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.58 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.7 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.6 |
Solubility | 30.1 mg/ml ; 0.25 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.27 |
Solubility | 6.44 mg/ml ; 0.0536 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.83 |
Solubility | 17.9 mg/ml ; 0.149 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 |
2.0 |
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) |
1.35 |
* 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 |
---|---|---|
With chlorine; In n-heptane; | EXAMPLE II Preparation of Dimethyl 3,3'-Dithiodipropionate To a 2-liter, 3-necked, jacketed glass flask fitted with a stirrer, reflux consenser, a thermowell, a fritted glass bubbler for charging chlorine, and a stopcock in the bottom was charged 1000 milliliters of n-heptane and 240 grams (2.0 moles) of methyl 3-mercapto propionate. Chlorine gas (0.104 moles, 74 grams) was passed into the vigorously stirred reaction mixture from a continuously weighed cylinder over about a 30 minute period. The reaction temperature increased from about 20 C. initially to about 45 C. measured at the end of the chlorination period. In addition, the reaction solution became cloudy during the chlorination. After the chlorination was complete, the reaction mixture was cooled to about 25 C. by passing tap water through the jacket of the reaction flask. The bottom (product) phase was drained from the flask. | |
With sodium 4-methylbenzenesulfinate; silver carbonate; In 1,4-dioxane; at 120℃; for 0.166667h;Microwave irradiation; | General procedure: Aryl sulfinate metal salt (0.36 mmol or 0.18 mmol), PdCl2 (0.06 mmol), AgNO3(0.6 mmol), DMF/DMSO (v/v = 19/1, 2 mL), and thiol (0.3 mmol) were added to the microwave tube. The tube was sealed and stirred for 5 min at ambient temperature. The tube was then heated at 40W for 10 min at 120 C. After cooling down, the resulting suspensions were filtered off and washed with CH2Cl2. A small amount of silica gel was added into the filtrate, and then evaporated. The residue was purified by flash chromatography on silica with hexane/EA to provide the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | EXAMPLE 1 Preparation of Isothiazolone.HCl salts Into a one-liter, 4-necked, round bottom flask equipped with a mechanical stirrer, thermometer, gas dispersion tube, and dry ice condenser with nitrogen inlet adapter, was placed methyl-3-mercaptopropionate (504.7 g, 4.20 mol). The vessel was purged with nitrogen and the liquid was cooled to 10 C. Monomethylamine (163.0 g, 5.25 mol) was added through the gas dispersion tube with stirring at 10-20 C. over a one hour period. Following the addition, the mixture was stirred at 20 C. for 20 hours to complete the reaction. Unreacted monomethylamine and the methanol by-product was then removed under reduced pressure (100 mmHg). The resultant mixture was then further reduced on a rotary evaporator to give crude N-methyl-3-mercaptopropionamide (500.8 g, 100% yield). A one-liter, 5-necked, jacketed resin kettle was equipped with an agitator, fritted glass dispersion tube, thermometer, condenser attached to an off-gas scrubber, and a feed line for N-methyl-3-mercaptopropionamide slurry. The jacket was connected to a temperature control bath for coolant circulation. The cooling system maintained the reaction temperature at 25-30 C. The flask was charged with 59.5 g of ethyl acetate. | |
100% | Step 1: Preparation of N-methyl-3-mercaptopropionamide (MMPA) Into a one-liter, 4-necked flask equipped with a mechanical stirrer, thermometer, gas dispersion tube, and dry ice condenser with nitrogen inlet adapter, was placed methyl-3-mercaptopropionate (MMP, 504.7 g, 4.20 mol). The vessel was purged with nitrogen and the liquid was cooled to 10 C. Monomethylamine (163.0 g, 5.25 mol) was added through the gas dispersion tube with stirring at 10-20 C. over 1 hr. After completing the addition, the mixture was stirred at 20 C. for 20 hrs. to complete the reaction. At this time the methanol by-product and unreacted monomethylamine were distilled from the mixture at ~100 mmHg. The resulting mixture was rotary evaporated to give crude N-methyl-3-mercaptopropionamide (500.8 g, 100% yield), containing <30 ppm N-methyl-3-(N'-methyl)aminopropionamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With hydrogen sulfide; | EXAMPLE 8: METHYL 3,3'-DITHIODIPROPIONATE The same reactor as in example 1 is charged with 240 g of methyl 3-mercaptopropionate, 16 g of solid sulphur and 7 g of anhydrous Amberlyst A 21 resin. The mixture is stirred for one hour at ambient temperature. Then it is heated at 85° C. for one hour and a half. The disuphide (CH3 O--CO--CH2 CH2) 2 S2 is thus obtained with a yield of 96percent in relation to the sulphur added. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium carbonate; In N,N-dimethyl-formamide; at 20.0℃; for 16.0h; | To a solution of methyl 4-chloro-3-nitrobenzoate (4.53 g, 0.021 mol) and methyl 3- mercaptopropionate (2.78 g, 0.023 mol) in DMF (15 mL) was added anhydrous potassium carbonate (0.023 mol, 3.17g). After stirring at ambient temperature for 16 h, the reaction was quenched with ice water. The precipitated product was filtered, washed well with water and dried under vacuum to give the title compound as a bright yellow solid (6.11 g,97%) which was used without further purification: LC/MS (ES) m/z 300 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 125℃; | fe/f-Butyl-(5-bromo-1 ,3-thiazol-2-yl)carbamate (12 g, 43.17 mmol, 1 eq.), 3-mercapto propionic acid methylester (5.7 g, 47.4 mmol, 1.1 eq.), tris(dibenzylidene acetone)di Pd(0) (1 g, 1 .07 mmol, 0.025 eq.), 9,9'-dimethyl-4,5-bis(diphenyl phosphino) xanthene (1 .24 g, 2.15 mmol, 0.05 eq.) and Lambda/,/V-diisopropyl ethyl amine (1 1 .15 g, 86.34 mmol, 2 eq.) are taken in degassed 1 ,4-dioxane (200 mL) in a pressure tube and heated under sealed condition at 125C overnight. Reaction mixture is filtered through celite, concentrated under vacuum and purified by flash chromatography to afford 9.5 g (69%) of the product. 1H NMR (DMSO-c/6, 400 MHz): delta 1 1 .64 (bs, 1 H), 7.38 (s, 1 H), 3.58 (s, 3H), 2.90-2.87 (t, J = 6.8 Hz, 2H), 2.59- 2.55 (t, J = 6.9 Hz, 2H), 1 .46 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen sulfide; sodium sulfite; In water; at 50 - 55℃; under 760.051 Torr; for 10.25h; | To a 1000 mL flask were added 280.0 g (1.15 mol) of <strong>[15441-06-2]dimethyl 3,3'-dithiodipropionate</strong>, 106.5 g (0.845 mol) of anhydrous Na2SO3, and 296.0 g of water. The reaction mixture was warmed to a temperature of 50°C-55°C in water bath. H2S (about 0.025 L/min) was introduced into the above reaction mixture for a total of 10 h. After the reaction was carried out under atmospheric pressure for 1 h (began from the introduction of H2S), 80.0 g (0.635 mol) of Na2SO3 was added to the reaction mixture in 8 aliquots and each aliquot, i.e. 10.0 g of Na2SO3 was added every half hour. After the introduction of H2S was stopped, the reaction temperature was maintained for 15 min. The reaction liquid was filtered under suction, and the filtrate was layered. The oil layer was washed with water, and then layered again. The resulting oil layer was distilled under reduced pressure with a circulating water pump to give methyl 3-mercapto propionate. [0031] The contents of methyl 3-mercapto propionate, <strong>[15441-06-2]dimethyl 3,3'-dithiodipropionate</strong> and dimethyl 3,3'-trithiodipropionate were measured at different time points by gas chromatography and plotted. The results were shown in figure 1. [0032] It can be seen from figure 1 that the content of target product methyl 3-mercapto propionate was relatively high, and was about 66.5percent at 6.5 h. [0033] It can also be seen from figure 1 that the content of methyl 3-mercapto propionate increased rapidly from the beginning of the reaction to the 5.5th h, and it tended to increase slowly or even decrease after the reaction was carried out for 5.5 h. Therefore, in view of cost-benefit, the reaction time ranging from 5.5 h to 7.5 h is optimal |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50%Chromat. | With silver(I) acetate; palladium dichloride; In dimethyl sulfoxide; N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave irradiation; | General procedure: Aryl sulfinate metal salt (0.36 mmol or 0.18 mmol), PdCl2 (0.06 mmol), AgNO3(0.6 mmol), DMF/DMSO (v/v = 19/1, 2 mL), and thiol (0.3 mmol) were added to the microwave tube. The tube was sealed and stirred for 5 min at ambient temperature. The tube was then heated at 40W for 10 min at 120 °C. After cooling down, the resulting suspensions were filtered off and washed with CH2Cl2. A small amount of silica gel was added into the filtrate, and then evaporated. The residue was purified by flash chromatography on silica with hexane/EA to provide the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37%Chromat. | With silver nitrate; palladium dichloride; In dimethyl sulfoxide; N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave irradiation; | General procedure: Aryl sulfinate metal salt (0.36 mmol or 0.18 mmol), PdCl2 (0.06 mmol), AgNO3(0.6 mmol), DMF/DMSO (v/v = 19/1, 2 mL), and thiol (0.3 mmol) were added to the microwave tube. The tube was sealed and stirred for 5 min at ambient temperature. The tube was then heated at 40W for 10 min at 120 °C. After cooling down, the resulting suspensions were filtered off and washed with CH2Cl2. A small amount of silica gel was added into the filtrate, and then evaporated. The residue was purified by flash chromatography on silica with hexane/EA to provide the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76%Chromat. | With silver carbonate; palladium dichloride; In tetrahydrofuran; at 120℃; for 0.166667h;Microwave irradiation; | General procedure: Aryl sulfinate metal salt (0.36 mmol or 0.18 mmol), PdCl2 (0.06 mmol), AgNO3(0.6 mmol), DMF/DMSO (v/v = 19/1, 2 mL), and thiol (0.3 mmol) were added to the microwave tube. The tube was sealed and stirred for 5 min at ambient temperature. The tube was then heated at 40W for 10 min at 120 °C. After cooling down, the resulting suspensions were filtered off and washed with CH2Cl2. A small amount of silica gel was added into the filtrate, and then evaporated. The residue was purified by flash chromatography on silica with hexane/EA to provide the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88%Chromat. | With silver nitrate; palladium dichloride; In dimethyl sulfoxide; N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave irradiation; | General procedure: Aryl sulfinate metal salt (0.36 mmol or 0.18 mmol), PdCl2 (0.06 mmol), AgNO3(0.6 mmol), DMF/DMSO (v/v = 19/1, 2 mL), and thiol (0.3 mmol) were added to the microwave tube. The tube was sealed and stirred for 5 min at ambient temperature. The tube was then heated at 40W for 10 min at 120 °C. After cooling down, the resulting suspensions were filtered off and washed with CH2Cl2. A small amount of silica gel was added into the filtrate, and then evaporated. The residue was purified by flash chromatography on silica with hexane/EA to provide the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 18-crown-6 ether; potassium carbonate; In acetonitrile; for 12h;Reflux; | General procedure: A mixture of 2-chloro-4-(trifluoromethyl)-benzonitrile (1.00 mmol) and appropriate thiol (RSH, 3.00 mmol),18-crown-6-ether (cat.) and potassium carbonate (2.00 mmol)were dissolved in acetonitrile (3 ml). The mixture was refluxedfor 12 h and then cooled to ambient temperature. The mixturewas quenched by adding water and extracted with EtOAc.Extracted organic compound was dried over MgSO4, filtered, andconcentrated in vacuo. The residue was purified by flash columnchromatography on silica gel using EtOAc/hexane (1:4) eluantcondition. (RSH = CH3CO2(CH2)2SH for 42). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With triethylamine; In acetonitrile; at 65℃; for 120h;Inert atmosphere; | General procedure: Dichlorodipyrrin (1 eq.) and dry acetonitrile were placed to three necked round bottom flask equipped with magnetic stirring bar, stoppered by rubber septa and flushed with argon via needles. Then a solution of the nucleophile (ca. 4 eq.) in CH3CN and triethylamine (ca. 6 eq.) have been added by the syringe, reaction flask was immersed into an oil bath heated to 65°C (unless otherwise specified). After a specified time period, the solvent was removed on rotary evaporator, the residue was dried on the vacuum line at 5*10?2Torr at 80?90°C to remove the base and one of the substrates and processed as cited below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With triethylamine; In acetonitrile; at 70℃; for 21h;Inert atmosphere; | General procedure: Dichlorodipyrrin (1 eq.) and dry acetonitrile were placed to three necked round bottom flask equipped with magnetic stirring bar, stoppered by rubber septa and flushed with argon via needles. Then a solution of the nucleophile (ca. 4 eq.) in CH3CN and triethylamine (ca. 6 eq.) have been added by the syringe, reaction flask was immersed into an oil bath heated to 65°C (unless otherwise specified). After a specified time period, the solvent was removed on rotary evaporator, the residue was dried on the vacuum line at 5*10?2Torr at 80?90°C to remove the base and one of the substrates and processed as cited below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61.5% | With tris-(dibenzylideneacetone)dipalladium(0); N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃;Inert atmosphere; | A mixture of the compound 9a (1.00g, 4.72mmol), methyl 3-mercaptopropanoate (1.13g, 9.40mmol), Pd2 (dba) 3 (0.15g, 0.16mmol), Xantphos (0.20g, 0.35mmol) and DIEA (1.23g, 9.52mmol) in dioxane (25mL) was stirred overnight at 100 C under N2. the solvent was removed under reduced pressure, the residue was purified by column chromatography to afford the compound 9b (0.73g, 61.5%). MS: 252 (M+H) +. |
61.5% | With tris-(dibenzylideneacetone)dipalladium(0); N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃;Inert atmosphere; | Compound 9a (1.00 g, 4.72 mmol), 3-mercaptopropionic acid methyl ester (1.13 g, 9.40 mmol),Pd2(dba)3 (0.15 g, 0.16 mmol), Xantphos (0.20 g, 0.35 mmol),DIEA (1.23 g, 9.52 mmol) was added in a nitrogen atmosphere in 1,4-dioxane (25 mL), stirred overnight at 100 C, concentrated under reduced pressure, the residue was purified by column chromatography to give Compound 9b (0.73 g, 61.5%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1,8-diazabicyclo[5.4.0]undec-7-ene; at 80℃; for 6h; | A separable four-necked flask was equipped with a thermometer and a reflux tube,The interior was made a nitrogen atmosphere.Into the four-necked flask,Component A and component B were charged according to the composition shown in Table 1,1 part by weight of a catalyst (1.8-diazabicyclo [5,4,0] undeca-7-ene,Wako Pure Chemical Industries, Ltd.) was added,The mixture was reacted at 80 C. for 6 hours,Examples 1 to 6 and Comparative Example 1 were obtained.The viscosity at 25 C. after the reaction in Examples 1 to 6 and Comparative Example 1 is also shown in Table 1.The clay was measured using an R type viscometer manufactured by Toki Sangyo Co., Ltd |
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