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Structure of Thiobenzamide
CAS No.: 2227-79-4
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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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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 2227-79-4 |
Formula : | C7H7NS |
M.W : | 137.20 |
SMILES Code : | NC(C1=CC=CC=C1)=S |
MDL No. : | MFCD00008060 |
InChI Key : | QIOZLISABUUKJY-UHFFFAOYSA-N |
Pubchem ID : | 683563 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H301 |
Precautionary Statements: | P301+P310 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅲ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.91 |
TPSA ? Topological Polar Surface Area: Calculated from |
58.11 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.48 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.49 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.71 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.45 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.69 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.06 |
Solubility | 1.2 mg/ml ; 0.00878 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.32 |
Solubility | 0.66 mg/ml ; 0.00481 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.16 |
Solubility | 0.949 mg/ml ; 0.00692 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) |
Yes |
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 |
-6.08 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) |
1.0 |
* 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 |
---|---|---|
78% | at 140℃; for 0.333333h;Neat (no solvent); | tert-Butyl 3-bromor4-oxopiperidine-l-carboxylate (1.0 g, 3.6 mmol) and benzothioamide (490 mg, 3.6 mmol) were heated neat at 1400C for 10 minutes. After cooling down, the resulting brown solid was sonicated in AcOEt for 10 minutes. Filtration and drying yielded 2-phenyl-4, 5, 6, 7- tetrahydrothiazolo [5, 4-c] pyridine hydrobromide as a brown solid (829 mg, 78percent): 1H NMR (400 MHz, DMSO-d6) delta 3.06-3.12 (m, 2H), 3.49-3.57 (m, 2H), 4.46-4.53 (m, 2H), 7.50-7.56 (m, 3H), 7.90-7.94 (m, 2H), 9.35 (br, 2H); m/z (APCI pos) 217.1 (10percent) [M+H] . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | In ethanol; | Step 20a A solution of alpha-formyl-alpha-chloroacetate (9.34 g, 49.5 mmol, 1 eq) and thiobenzamide (6.79 g, 49.5 mmol, 1 eq) in EtOH (37.0 mL) is refluxed for 1 hr. The solution changes from an orange/brown color to a deep green. This solution is washed with water and extracted with CH2Cl2. The organic fraction is dried over Na2SO4, filtered, and the solvent removed in vacuo. The product is purified by column chromatography using a Biotage Flash 40M column (20% hexanes/EtOAc) to give ethyl 2-phenyl-thiazole-5-carboxylate as a deep orange oil (1.82 g, 15%). MS (ESI) for C12H13NO3S m/z 252.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In water; benzene; | Stage A: 2-phenyl-5-carbethoxy-thiazole A solution of ethyl formyl beta chloracetate in 240 ml of benzene was added to a suspension of 78 g of thiobenzamide in 200 ml of benzene and the mixture was refluxed for 3 hours 30 minutes while eliminating the water formed. The reaction medium was cooled and 320 ml of a 20% solution of potassium carbonate and 220 ml of water were added slowly. Extraction was carried out with ether, followed by washing, drying and distillation under reduced pressure to obtain 75.5 g of the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In 1,4-dioxane; for 2h;Heating / reflux; | Step 1. 2-Phenyl-thiazole-4-carboxylic acid A solution of thiobenzamide (Aldrich; 1.37 g, 10 mmol) and 3-bromopyruvic acid (1.67 g, 10 mmol) in dioxane (50 mL) was heated at reflux for 2 hrs. The solution was concentrated in vacuo. Water (50 mL) was added. The resulting solid was filtered and triturated with ether to give a white solid (2.0 g, 99%). |
0.8 g | In 1,4-dioxane; at 110℃; for 2h; | To a solution of 1-1 (1.0 g, 7.3 mmol) and 3-bromopyruvic acid (1.2 g, 7.3 mmol) in 1,4-dioxane (50 mL). The reaction mixture was stirred at 110 C. for 2 hours. The mixture was quenched with ice water (100 mL), extracted with EtOAc, washed with brine, dried with anhydrous Na2SO4, filtered and concentrated to give the crude product. The crude product was purified by silica gel chromatography eluted to give product 1-2 (0.8 g, 53.5). MS m/z [ESI]: 206.0 [M+1]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45.9% | With magnesium sulfate heptahydrate; In toluene; at 100℃; for 4h; | To a solution of 1-2 (4.5 g, 30.0 mmol) and thiobenzamide (4.1 g, 30.0 mmol) in toluene (50 mL) was added magnesium sulfate heptahydrate (7.2 g, 59.8 mmol). The reaction mixture was stirred at 100 C. for 4 hours and quenched with ice water (100 mL), extracted with ether, washed with brine, dried with anhydrous Na2SO4, filtered and concentrated to give the crude product. The crude product was purified by silica gel chromatography eluted to give product 1-3 (3.2 g, 45.9%). MS m/z [ESI]: 234.1 [M+1]. |
35% | With magnesium sulfate; In toluene; at 90℃; for 16h;Inert atmosphere; | To a stirring solution of benzothioamide (25 g, 182.48 mmol) in toluene (250 mL) under inert atmosphere were added ethyl 2-chloro-3-oxopropanoate 96 (41.15 g, 274.34 mmol), anhydrous magnesium sulfate (65.85 g, 547.44 mmol) at room temperature and heated to 90 oC and stirred for 16 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to obtain the crude. The crude was purified through silica gel column chromatography using 10% EtOAc/ hexanes to afford compound 111 (15 g, 35%) as pale yellow solid. TLC: 20% EtOAc/ hexanes (Rf: 0.8); 1H NMR (400 MHz, DMSO-d6): delta 8.49 (s, 1H), 8.04-8.01 (m, 2H), 7.58-7.51 (m, 3H), 4.34 (q, J = 7.2 Hz, 2H), 1.32 (t, J = 7.1 Hz, 3H); LCMS Calculated for C12H11NO2S: 233.05; LCMS observed: 234.1 (M+1)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | In 1,4-dioxane; water; at 80℃; for 1h; | Ethyl-3-ethoxyacryalate (4.0 g, 27.7 mmol) was dissolved in dioxane-H2O (30 ml, 1:1 v/v) and cooled to -10 C. N-Bromosuccinimide (5.43 g, 30.5 mmol) was added to this solution and the reaction mixture was allowed to warm up to room temperature and further stirred for 1 h. Thiobenzamide (3.8 g, 27.7 mmol) was then added and the reaction mixture was further heated to 80 C for 1 h. The reaction mixture was then cooled to room temperature and quenched with aqueous ammonia solution. The organic product was extracted with EtOAc and combined extracts were washed with H2O and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 5-10% EtOAc in petroleum ether) to afford ethyl 2-phenylthiazole-5-carboxylate (1.1 g, yield 17%) as a yellow solid. 1H NMR (300 MHz, CDCl3) delta 8.43 (s, 1 H), 8.01 - 7.98 (m, 2H), 7.48 - 7.48 (m, 3H), 4.44 - 4.37 (q, J = 7.2 Hz, 2H), 1.44 - 1.39 (t, J = 7.2 Hz, 3H). MS (ESI) m/z: Calculated for C12H11NO2S: 233.05; found: 234.0 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | To a solution of (E)-ethyl 3-ethoxyacrylate (12.6 g, 87.6 mmol) in 1,4-dioxane (50 mL) and water (50 mL) was added NBS (17.2 g, 96.4 mmol) at 0C. The mixture was stirred for 1 hour at room temperature. Benzothioamide (12.1 g, 87.6 mmol) was added and the mixture was stirred for 1 hour at 80-90C. The reaction mixture was cooled down to room temperature and poured into NH4OH (300 mL, 3% in water) and extracted with ethyl acetate (150 mL x 2), dried over sodium sulfate, concentrated and purified by chromatography (PE:EA =10/1) to give compound 10-la (2.9 g, 14% yield); LCMS (ESI): m/z 234 [M+Hf?. |
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