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Structure of 10191-60-3
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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. : | 10191-60-3 |
Formula : | C4H6N2S2 |
M.W : | 146.23 |
SMILES Code : | N#CN=C(SC)SC |
MDL No. : | MFCD00009825 |
InChI Key : | IULFXBLVJIPESI-UHFFFAOYSA-N |
Pubchem ID : | 66289 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H314 |
Precautionary Statements: | P260-P264-P270-P280-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P363-P405-P501 |
Class: | 8 |
UN#: | 1759 |
Packing Group: | Ⅲ |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.96 |
TPSA ? Topological Polar Surface Area: Calculated from |
86.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.93 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.93 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.38 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.07 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.37 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.83 |
Solubility | 2.16 mg/ml ; 0.0148 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.38 |
Solubility | 0.0616 mg/ml ; 0.000421 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.03 |
Solubility | 13.6 mg/ml ; 0.0927 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 |
-5.82 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 |
3.0 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) |
3.59 |
* 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% | With sodium carbonate In water at 10 - 20℃; for 2 h; | Example 1Into a solution of 26.5 g of sodium carbonate in 150 ml of water are metered, at room temperature, 28.8 g of cysteamine hydrochloride. The reaction mixture is cooled to 100C and 37.1 g of dimethyl N-cyanocarbonimidodithiocarbonate are metered in. After the end of the metered addition, the mixture is stirred at 1O0C for a further 2 hours and then heated to 200C. At 200C, 37 g of 20percent hydrochloric acid are added dropwise. The mixture is then filtered and the solids are washed with 100 ml of water. After drying under reduced pressure, 30.3 g of cyanimino-l,3-thiazolidine are obtained (corresponds to a yield of 94.7percent).Example 2Into a solution of 26.5 g of sodium carbonate in 150 ml of water are metered, at room temperature, 28.8 g of cysteamine hydrochloride. The reaction mixture is cooled to 100C and 37.1 g of dimethyl N-cyanocarbonimidodithiocarbonate are metered in. After the end of the metered addition, the mixture is stirred at 1O0C for a further 2 hours and then heated to 200C. The mixture is subsequently filtered and the solids are washed with 2 x 100 ml of water. After drying under reduced pressure, 29.8 g of cyanimino-l,3-thiazolidine are obtained (corresponds to a yield of 93 percent). |
92% | With sodium hydrogencarbonate In water at 10 - 20℃; for 3 h; | Example 3Into a solution of 23.8 g of sodium hydrogencarbonate in 200 ml of water are metered, at room temperature, 28.8 g of cysteamine hydrochloride. The reaction mixture is cooled to 100C and 37.1 g of dimethyl N-cyanocarbonimidodithiocarbonate are metered in. After the end of the metered addition, the mixture is stirred at 100C for a further 3 hours and then heated to 200C. The mixture is then filtered and the solids are washed with 100 ml of water. After drying under reduced pressure, 29.4 g of cyanimino-l,3-thiazolidine are obtained (corresponds to a yield of 92percent). |
87.5% | With sodium hydroxide In water at 0 - 10℃; for 0.666667 h; | Add 300 ml of water to the three-necked bottle, then add 16.4 g of sodium hydroxide, stir and dissolve,Cool down to below 10 °C,Rapid addition of cysteamine hydrochloride 56g (0.50 mol),After stirring and dissolving,The temperature was lowered to 0 to 5 ° C, and then a compound HRB-1365-0 (cyanimide dimethyl ester molecular formula: C4H6N2S2) 61 g (0.41 mol) was added, and after stirring for 40 minutes, the reaction was completed and filtered.The filter cake was washed with 200 ml of water, the filter cake was white solid, and the wet product was 57 g.Drying under reduced pressure at 60-65 ° C gave a white crystalline solid 46 g.That is, the compound HRB-1365-2 (2-cyanoimido-1,3-thiazolidine molecular formula: C4H5N3S),The yield was 87.5percent, and the HPLC (High Performance Liquid Chromatograph) content was ≥99percent. |
85.8% | Stage #1: With sodium methylate In methanolInert atmosphere Stage #2: at 0 - 5℃; Inert atmosphere Stage #3: With hydrogenchloride In methanol; water at 20 - 40℃; Inert atmosphere |
EXAMPLE 3; A 1 litre four-necked flask provided with a thermometer and stirrer is charged with 9Og of methanol (2.815 moles) and 36g of sodium methoxide (0.667 moles, 1.3 mole equivalent based upon 1.1 mole equivalent of 2-aminoethane thiol hydrochloride) under nitrogen. The mixture is cooled and stirred to dissolve in <n="16"/>methanol, then 63.5g of 2-aminoethane thiol hydrochloride (0.564 moles) is added thereto and dissolved therein. The reaction mixture is cooled to 0° C and 75g of dimethyl N-cyanoiminodithiocarbonate (0.514 moles) is added keeping the inside temperature at 5° C or less. After the end of addition, the mixture is allowed to react at 0 to 5° C for 2 hours under nitrogen. Thereafter, the reaction mixture is heated to 20° C and pH is adjusted to 4 with aqueous hydrochloric acid solution (36percent w/w), then further heated to 40° C and stirred for 2 hours. After stirring, the reaction mixture is cooled to 0° C and the crystals are suction filtered and the slurry thus obtained is washed with 225ml of chilled water to obtain 66g of 2-cyanoimino-l, 3-thiazolidine. The wet crystals are dried in vacuo at 80° C under reduced pressure for 5 hours to obtain 58g of 2-cyanoimino-l, 3-thiazolidine (yield 85.8percent) with 99.9percent HPLC purity. |
81.6% | Stage #1: With sodium hydroxide In water Stage #2: for 2 h; Stage #3: With hydrogenchloride In water at 20 - 40℃; for 2 h; |
Example 1 A 300 ml four-necked flask provided with a thermometer and an agitator was charged with 150 g of water (8.3 moles), then 11.2 g of 99percent by weight sodium hydroxide (0.28 mole, 1.12 moles based upon 1 mole of 2-aminoethane thiol hydrochloride) was added while cooling and agitating to be dissolved in the water, then 28.8 g of 99.5percent by weight 2-aminoethane thiol hydrochloride (0.25 mole) was added thereto and dissolved therein, then the reaction mixture was cooled to 0°C. To this reaction mixture, 36.9 g of 99.5percent by weight dimethyl N-cyanoiminodithiocarbonate ester (0.25 mole) was added so that the temperature inside the system became 5°C or less.. After the end of addition, the mixture was allowed to react at 0 to 5°C for 2 hours. Thereafter, the reaction mixture was heated to 20°C, adjusted in PH to 4.0 with 36percent by weight aqueous hydrochloric acid solution, then further heated to 40°C and allowed to age for 2 hours. After aging, the reaction mixture was cooled to 20°C, then the crystals were suction filtered and washed with 100 g of water (5.6 moles) to obtain 36.6 g of 2-cyanoimino-1,3-thiazolidine. The wet crystals were dried in vacuo at 84°C under 6.7 x 10-4 MPa for 5 hours to obtain 28.6 g of 99.7percent purity 2-cyanoimino-1,3-thiazolidine (yield 89.8percent = value converted to purity, based on the charged dimethyl N-cyanoiminodithiocarbonate ester). Note that the purity was analyzed by means of high pressure liquid chromatography (HPLC). Example 2; A 300 ml four-necked flask provided with a thermometer and an agitator was charged with 150 g of water (8.3 moles), then 12.3 g of 99percent by weight sodium hydroxide (0.31 mole, 1.24 moles based upon 1 mole of 2-aminoethane thiol hydrochloride) was added, while cooling and agitating to be dissolved in the water, then 28.8 g of 99.5percent by weight 2-aminoethane thiol hydrochloride (0.25 mole) was added thereto and dissolved therein. Thereafter, the reaction mixture was cooled to 0°C., then 36.9 g of 99.5percent by weight dimethyl N-cyanoiminodithiocarbonate ester (0.25 mole) was gradually added so that the temperature inside the system became 5°C or less. After the end of addition, the mixture was allowed to react for further 2 hours. Next, the reaction mixture was heated to 20°C, adjusted in pH to 3.9 with 4.56 g (0.045 mole) of 36percent by weight aqueous hydrochloric acid solution, then further heated to 40°C and allowed to age for 2 hours. After aging, the reaction mixture was cooled to 20°C, then suction filtered and washed with 200 g of water (11.1 moles) to obtain 34.7 g of wet crystals of 2-cyanoimino-1,3-thiazolidine. The wet crystals obtained above, were dried in vacuo at 80°C under 6.7 x 10-4 MPa for 5 hours to obtain 27.9 g of 100percent purity 2-cyanoimino-1,3-thiazolidine (yield 87.9percent = value converted to purity, based on charged dimethyl N-cyanoiminodithiocarbonate ester). Further, the total weight of the filtrate combined with the washings was 371.5 g. The filtrate included 0.98percent of 2-cyanoiminothiazolidine (value converted to yield: 11.5percent). Example 3; A 300 ml four-necked flask provided with a thermometer and an agitator was charged with 150 g of water (8.3 moles), then 10.6 g of 99percent by weight sodium hydroxide (0.26 mole, 1.04 moles based upon 1 mole of 2-aminoethane thiol hydrochloride) was added, while cooling and agitating to be dissolved in the water, then 28.8 g of 99.5percent by weight 2-aminoethane thiol hydrochloride (0.25 mole) was added thereto and dissolved therein. Thereafter, the reaction mixture was cooled to 0°C, then 36.9 g of 99.5percent by weight dimethyl N-cyanoiminodithiocarbonate ester (0.25 mole) was gradually added so that the temperature inside the system became 5°C or less, then was allowed to react for 2 hours. Next, the reaction mixture was heated to 20°C, adjusted in pH to 9.2 with 0.25 g of 36percent by weight aqueous hydrochloric acid solution (0.0025 mole), then further heated to 40°C and allowed to age for 2 hours. After aging, the reaction mixture was cooled to 20°C, then suction filtered and washed with 200 g of water (11.1 moles) to obtain 36.33 g of wet crystals of 2-cyanoimino-1,3-thiazolidine. The wet crystals were dried in vacuo at 80°C under 6.7 x 10-4 MPa for 5 hours to obtain 27.2 g of 95.2percent purity 2-cyanoimino-1,3-thiazolidine (yield 81.6percent = value converted to purity, based on the charged dimethyl N-cyanoiminodithiocarbonate ester). Further, the total weight of the filtrate combined with the washings was 361.5 g. The filtrate included 0.95percent of 2-cyanoiminothiazolidine (value converted to yield: 10.8percent). |
59.4% | Stage #1: With sodium hydroxide In water Stage #2: for 2 h; Stage #3: With hydrogenchloride In water |
Comparative Example 2 A 300 ml four-necked flask provided with a thermometer and an agitator was charged with 114 g of water (6.3 moles), then 20.9 g of 99percent by weight sodium hydroxide (0.50 mole) was added, while cooling and agitating, to be dissolved therein, then 28.8 g of 99.5percent by weight 2-aminoethane thiol hydrochloride (0.25 mole) was added thereto and dissolved therein.. Then, the reaction mixture was cooled to 0°C, then 36.9 g of 99.5percent by weight dimethyl N-cyanoiminodithiocarbonate ester (0.25 mole) was gradually added, while holding the temperature to 5°C or less, then the mixture was allowed to react for 2 hours. Next, 30.9 g of 36percent by weight aqueous hydrochloric acid solution (0.29 mole) was added to try to adjust the PH, but the mixture violently started bubbling at around PH 9.0 and finally the PH became 9.5.. Next, the reaction mixture was suction filtered and washed with 200 g of water (11.1 moles) to obtain 28.6 g of wet crystals of 2-cyanoimino-1,3-thiazolidine. The wet crystals were dried in vacuo at 80°C under 6.7 x 10-4 MPa for 5 hours to obtain 18.9 g of 100percent purity 2-cyanoimino-1,3-thiazolidine (yield 59.4percent = value converted to purity, based on the charged dimethyl N-cyanoiminodithiocarbonate ester). Comparative Example 3; A 300 ml four-necked flask provided with a thermometer and an agitator was charged with 150 g of water (8.3 moles), then 20.9 g of 99percent by weight sodium hydroxide (0.50 mole) was added, while cooling and agitating, to be dissolved, then 28.8 g of 99.5percent by weight 2-aminoethane thiol hydrochloride (0.25 mole) was added thereto and dissolved therein. Thereafter, the reaction mixture was cooled to 0°C, then 36.9 g of 99.5percent by weight dimethyl N-cyanoiminodithiocarbonate ester (0.25 mole) was gradually added, while holding the temperature to 5°C or less, the mixture was then allowed to react for 2 hours. Next, 31.7 g of 36percent by weight aqueous hydrochloric acid solution (0.31 mole) was added to try to adjust the pH, but the mixture violently started bubbling at around pH 9.0 and finally the pH became 1.7. Next, the reaction mixture was suction filtered and washed with 200 g of water (11.1 moles) to obtain 34.8 g of wet crystals of 2-cyanoimino-1,3-thiazolidine. The wet crystals were dried in vacuo at 80°C under 6.7 x 10-4 MPa for 5 hours to obtain 20.7 g of 100percent purity 2-cyanoimino-1,3-thiazolidine (yield 65.2percent = value converted to purity, based on the charged dimethyl N-cyanoiminodithiocarbonate ester). |
47.7% | Stage #1: With sodium hydroxide In water Stage #2: for 3 h; Heating / reflux |
Comparative Example 1 A 300 ml four-necked flask provided with a thermometer and an agitator was charged with 100 g of water (5.6 moles), then 10.1 g of 99percent by weight sodium hydroxide (0.25 mole) was added, while cooling and agitating to dissolve it.. Next, 28.8 g of 99.5percent by weight 2-aminoethane thiol hydrochloride (0.25 mole) was added thereto and dissolved therein, then 36.9 g of dimethyl N-cyanoiminodithiocarbonate ester (0.25 mole) was added and the mixture was heated and refluxed under agitation for 3 hours.. After the end of the reaction, the reaction mixture was cooled to room temperature, then the crystals were suction filtered and washed with methanol and dried in vacuo at 80°C under 6.7 x 10-4MPa for 5 hours to obtain 15.2 g of 99.7percent purity 2-cyanoimino-1,3-thiazolidine (yield 47.7percent = value converted to purity, based on the charged dimethyl N-cyanoiminodithiocarbonate ester). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.1% | for 3 h; Heating / reflux | Reference Example 1 To 500 ml of ethanol 146.24 g of dimethyl N-cyanoiminodithiocarbonate ester (1 mole) and 77.15 g of 2-aminoethane thiol (1 mole) were added.. The mixture was heated and refluxed under agitation for 3 hours.. After the end of the reaction, the mixture was cooled to room temperature, then the precipitated crystals were filtered.. The crystals thus obtained were washed with ethanol, then dried to obtain 85.25 g of the above compound. (If making the purity of the above product 100percent, the yield of the N-cyanoiminothiazolidine becomes 67.1percent.) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With diisopropylamine In N,N-dimethyl-formamide at 100℃; for 5 h; | The synthesis of ethyl 4-amino-2-(methylthio)thiazole-5-carboxylate Ethyl 2-mercaptoacetate (50 g, 0.416 mol) was dissolved in 500 ml of dimethylformamide and added with dimethyl N-thienodithioimino carbonate (67 g, 0.416 mol) and diisopropylamine (112 ml, 0.624 mol). After heating at 100° C. for 5 hours, the mixture was extracted with 500 ml of saturated ammonium chloride and 500 ml of ethylacetate, dried with sodium sulfate, filtered and concentrated under vacuum. After washing the solid with n-hexane, the title compound (90 g, 99percent) was obtained. 1H-NMR (400 MHz, CDCl3); δ 5.84 (brs, 2H), 4.26 (q, J=7.2 Hz, 2H), 2.63 (s, 3H), 1.32 (t, J=7.2 Hz, 3H); LC-MS 219 (MH+) |
89% | With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 100℃; | Ethyl 2-mercaptoacetate (5 g, 42 mmol, 1.0 eq) was dissolved in DMF (50 mL) and added with N-thienodi-thioimino carbonate (6.1 g, 42 mmol, 1.0 eq) and DIPEA (16.3 g, 126 mmol, 3.0 eq). After heating at 100 °C for 5 h, the mixture was diluted with saturated aqueous ammonium chloride (100 mL) and extracted with EtOAc (100 mLx2). The combined organic layer was washed with brine, dried, concentrated. The solid was washed with n-hexane and dried under vacuum to give the title compound (8 g, yield: 89percent) as a yellow solid. ESI-MS (M+H)+: 219.0. |
A108788 [19975-56-5]
2-(Methylthio)-4,5-dihydrothiazole
Similarity: 0.55