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Structure of 2-Thiophenesulfonyl chloride
CAS No.: 16629-19-9
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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. : | 16629-19-9 |
Formula : | C4H3ClO2S2 |
M.W : | 182.65 |
SMILES Code : | O=S(C1=CC=CS1)(Cl)=O |
MDL No. : | MFCD00005426 |
InChI Key : | VNNLHYZDXIBHKZ-UHFFFAOYSA-N |
Pubchem ID : | 85518 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 37.4 |
TPSA ? Topological Polar Surface Area: Calculated from |
70.76 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.6 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.16 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.76 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.43 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.63 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.05 |
Solubility | 1.63 mg/ml ; 0.00895 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.24 |
Solubility | 1.05 mg/ml ; 0.00574 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.21 |
Solubility | 1.13 mg/ml ; 0.00621 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 |
-6.59 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 |
0.0 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) |
2.61 |
* 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 |
---|---|---|
34% | EXAMPLE 27 N-(4-Bromo-3-methyl-5-isoxazolyl)-2-thiophenesulfonamide N-(4-Bromo-3-methyl-5-isoxazolyl)-2-thiophenesulfonamide was prepared from <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> and 2-thiophenesulfonyl chloride according to the procedures described in Example 5. The crude product was purified by recrystallization from ethyl acetate/hexanes to give a crystalline solid, m.p. 125-127 C., yield 34%. | |
34% | EXAMPLE 67 N-(4-Bromo-3-methyl-5-isoxazolyl)-2-thiophenesulfonamide N-(4-Bromo-3-methyl-5-isoxazolyl)-2-thiophenesulfonamide was prepared from <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> and 2-thiophenesulfonyl chloride according to the procedures described in Example 45. The crude product was purified by recrystallization from ethyl acetate/hexanes to give a crystalline solid, m.p. 125-127 C., yield 34%. | |
With sodium hydroxide; In tetrahydrofuran; water; mineral oil; | EXAMPLE 9 N-(4-Bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (1 77 mg, 1.0 mmol) in dry tetrahydrofuran (THF, 2 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) in dry THF (1 ml) at 0-5 C. After stirring at 0-5 C. for 5 min., the reaction was stirred at room temperature for 10 min to complete the reaction. The reaction mixture was re-cooled to 0 C. and thiophene-2-sulfonyl chloride (200 mg, 1.1 mmol) dissolved in dry THF (2 ml) was added dropwise. Stirring was continued for 1 h; during this period the reaction mixture slowly attained ambient temperature. THF was removed under reduced pressure. The residue was dissolved in water (10 ml), the pH was adjusted to 10-11 by adding 5 N sodium hydroxide solution, and was extracted with ethyl acetate (3*10 ml) to remove the neutral impurities. The aqueous layer was acidified with concentrated HCl (pH 2-3) and extracted with methylene chloride (3*10 ml). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-(4-bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide. The pure material was obtained by recrystallization using hexanes/ethyl acetate (110 mg, 34% yield), m.p. 125-127 C. |
With sodium hydroxide; In tetrahydrofuran; water; mineral oil; | EXAMPLE 1 N-(4-Bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (177 mg, 1.0 mmol) in dry tetrahydrofuran (THF, 2 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) in dry THF (1 ml) at 0-5 C. After stirring at 0-5 C. for 5 min., the reaction was stirred at room temperature for 10 min to complete the reaction. The reaction mixture was re-cooled to 0 C. and thiophene-2-sulfonyl chloride (200 mg, 1.1 mmol) dissolved in dry THF (2 ml) was added dropwise. Stirring was continued for 1 h; during this period the reaction mixture slowly attained ambient temperature. THF was removed under reduced pressure. The residue was dissolved in water (10 ml), the pH was adjusted to 10-11 by adding 5 N sodium hydroxide solution, and was extracted with ethyl acetate (3*10 ml) to remove the neutral impurities. The aqueous layer was acidified with concentrated HCl (pH 2-3) and extracted with methylene chloride (3*10 ml). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-(4-bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide. The pure material was obtained by recrystallization using hexanes/ethyl acetate (110 mg, 34% yield), m.p. 125-127 C. | |
With sodium hydroxide; In tetrahydrofuran; water; mineral oil; | EXAMPLE 9 N-(4-Bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (177 mg, 1.0 mmol) in dry tetrahydrofuran (THF, 2 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) in dry THF (1 ml) at 0-5 C. After stirring at 0-5 C. for 5 min., the reaction was stirred at room temperature for 10 min to complete the reaction. The reaction mixture was re-cooled to 0 C. and thiophene-2-sulfonyl chloride (200 mg, 1.1 mmol) dissolved in dry THF (2 ml) was added dropwise. Stirring was continued for 1 h; during this period the reaction mixture slowly attained ambient temperature. THF was removed under reduced pressure. The residue was dissolved in water (10 ml), the pH was adjusted to 10-11 by adding 5 N sodium hydroxide solution, and was extracted with ethyl acetate (3*10 ml) to remove the neutral impurities. The aqueous layer was acidified with concentrated HCl (pH 2-3) and extracted with methylene chloride (3*10 ml). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-(4-bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide. The pure material was obtained by recrystallization using hexanes/ethyl acetate (110 mg, 34% yield), m.p. 125-127 C. | |
With sodium hydroxide; In tetrahydrofuran; water; mineral oil; | EXAMPLE 1 N-(4-Bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (177 mg, 1.0 mmol) in dry tetrahydrofuran (THF, 2 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) in dry THF (1 ml) at 0-5 C. After stirring at 0-5 C. for 5 min., the reaction was stirred at room temperature for 10 min to complete the reaction. The reaction mixture was re-cooled to 0 C. and thiophene-2-sulfonyl chloride (200 mg, 1.1 mmol) dissolved in dry THF (2 ml) was added dropwise. Stirring was continued for 1 h; during this period the reaction mixture slowly attained ambient temperature. THF was removed under reduced pressure. The residue was dissolved in water (10 ml), the pH was adjusted to 10-11 by adding 5 N sodium hydroxide solution, and was extracted with ethyl acetate (3*10 ml) to remove the neutral impurities. The aqueous layer was acidified with concentrated HCl (pH 2-3) and extracted with methylene chloride (3*10 ml). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-(4-bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide. The pure material was obtained by recrystallization using hexanes/ethyl acetate (110 mg, 34 % yield), m.p. 125-127 C. | |
With sodium hydroxide; In tetrahydrofuran; water; mineral oil; | EXAMPLE 1 N-(4-Bromo-3-methyl-5-isoxazolyl)thiophene-2-sulf onamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (177 mg, 1.0 mmol) in dry tetrahydrofuran (THF, 2 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) in dry THF (1 ml) at 0-5 C. After stirring at 0-5 C. for 5 min., the reaction was stirred at room temperature for 10 min to complete the reaction. The reaction mixture was re-cooled to 0 C. and thiophene-2-sulfonyl chloride (200 mg, 1.1 mmol) dissolved in dry THF (2 ml) was added dropwise. Stirring was continued for 1 h; during this period the reaction mixture was slowly attained the ambient temperature. THF was removed under reduced pressure. The residue was dissolved in water (10 ml), the pH was adjusted to 10-11 by adding 5N sodium hydroxide solution, and was extracted with ethyl acetate (3*10 ml) to remove the neutral impurities. The aqueous layer was acidified with concentrated HCl (pH 2-3) and extracted with methylene chloride (3*10 ml). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-(4-bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide. The pure material was obtained by recrystallization using hexanes/ethyl acetate (110 mg, 34 % yield), m.p. 125-127 C. | |
With sodium hydroxide; In tetrahydrofuran; water; mineral oil; | EXAMPLE 1 N-(4-Bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (177 mg, 1.0 mmol) in dry tetrahydrofuran (THF, 2 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) in dry THF (1 ml) at 0-5 C. After stirring at 0-5 C. for 5 min., the reaction was stirred at room temperature for 10 min to complete the reaction. The reaction mixture was re-cooled to 0 C. and thiophene-2-sulfonyl chloride (200 mg, 1.1 mmol) dissolved in dry THF (2 ml) was added dropwise. Stirring was continued for 1 h; during this period the reaction mixture slowly attained ambient temperature. THF was removed under reduced pressure. The residue was dissolved in water (10 ml), the pH was adjusted to 10-11 by adding 5 N sodium hydroxide solution, and was extracted with ethyl acetate (3*10 ml) to remove the neutral impurities. The aqueous layer was acidified with concentrated HCl (pH 2-3) and extracted with methylene chloride (3*10 ml). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-(4-bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide. The pure material was obtained by recrystallization using hexanes/ethyl acetate (110 mg, 34 % yield), m.p. 125-127 C. | |
With sodium hydroxide; In tetrahydrofuran; water; mineral oil; | EXAMPLE 9 N-(4-Bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (177 mg, 1.0 mmol) in dry tetrahydrofuran (THF, 2 mL) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) in dry THF (1 mL) at 0-5 C. After stirring at 0-5 C. for 5 min., the reaction was stirred at room temperature for 10 min to complete the reaction. The reaction mixture was re-cooled to 0 C. and thiophene-2-sulfonyl chloride (200 mg, 1.1 mmol) dissolved in dry THF (2 mL) was added dropwise. Stirring was continued for 1 h; during this period the reaction mixture slowly attained ambient temperature. THF was removed under reduced pressure. The residue was dissolved in water (10 mL), the pH was adjusted to 10-11 by adding 5N sodium hydroxide solution, and was extracted with ethyl acetate (3*10 mL) to remove the neutral impurities. The aqueous layer was acidified with concentrated HCI (pH 2-3) and extracted with methylene chloride (3*10 mL). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-(4-bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide. The pure material was obtained by recrystallization using hexanes/ethyl acetate (110 mg, 34% yield), m.p. 125-127 C. | |
With sodium hydroxide; In tetrahydrofuran; water; mineral oil; | EXAMPLE 1 N-(4-Bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (177 mg, 1.0 mmol) in dry tetrahydrofuran (THF, 2 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) in dry THF (1 ml) at 0-5 C. After stirring at 0-5 C. for 5 min., the reaction was stirred at room temperature for 10 min to complete the reaction. The reaction mixture was re-cooled to 0 C. and thiophene-2-sulfonyl chloride (200 mg, 1.1 mmol) dissolved in dry THF (2 ml) was added dropwise. Stirring was continued for 1 h; during this period the reaction mixture was slowly attained the ambient temperature. THF was removed under reduced pressure. The residue was dissolved in water (10 ml), the pH was adjusted to 10-11 by adding 5N sodium hydroxide solution, and was extracted with ethyl acetate (3*10 ml) to remove the neutral impurities. The aqueous layer was acidified with concentrated HCl(pH 2-3) and extracted with methylene chloride (3*10 ml). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-(4-bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide. The pure material was obtained by recrystallization using hexanes/ethyl acetate (110 mg, 34 % yield), m.p. 125-127 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.62 g (94%) | In tetrahydrofuran; | Step A: N-(1,1-Dimethylethyl)-2-thiophenesulfonamide To a solution of t-butylamine (8.35 g, 0.114 mol) in dry tetrahydrofuran (THF) (20 mL) cooled to 0 C. was added dropwise 2-thiophenesulfonyl chloride (5.0 g, 27.4 mmol). After the addition was completed, the reaction mixture was warmed to ambient temperature and stirred overnight. The mixture was extracted with ethyl acetate (3*80 mL) and the combined extracts were washed with water, dried over molecular sieves and concentrated. The residue was chromatographed on (silica, eluding with 25% ethyl acetate-hexane) to yield 5.62 g (94%) of solid: mp 80-82 C. |
5.62 g (94%) | In tetrahydrofuran; | Step A: N-(1,1-Dimethylethyl)-2-thiophenesulfonamide To a solution of t-butylamine (8.35 g, 0.114 mol) in dry tetrahydrofuran (THF) (20 mL) cooled to 0 C. was added dropwise 2-thiophenesulfonyl chloride (5.0 g, 27.4 mmol). After the addition was completed, the reaction mixture was warmed to ambient temperature and stirred overnight. The mixture was extracted with ethyl acetate (3*80 mL) and the combined extracts were washed with water, dried over molecular sieves and concentrated. The residue was chromatographed on silica, eluding with 25% ethyl acetate-hexane, to yield 5.62 g (94%) of solid: mp 80-82 C. |
In chloroform; at 0 - 20℃; for 1.16667h;Heating / reflux; | Thiophene-2-sulfonyl chloride (15 g, 0.082 mol) was dissolved in CHC13 (200 mL) under N2 atmosphere and then cooled to 0C. tert-Butylamine (25.9 mL, 0.246 mol) dissolved in CHC13 (50 mL) was then added dropwise to the reaction mixture. The reaction mixture was stirred for 1 h at room temperature and then at reflux for 10 min. Toluene (700 mL) was added and the organic phase was washed with water (3 x 50 mL), dried, and concentrated in vacuo. The sub-title product was used without further purification in the next step. IH NMR B (CDC13) : 7.60 (1H, dd, J= 1.3, 3.8 Hz), 7.53 (1H, dd, J= 1.3, 5.0 Hz), 7.02 (1H, dd, J = 5. 0,3. 8 Hz), 5.13 (1H, m), 1.24 (9H, m) 13C NMR B (CDC13) : 145.0, 131.7, 131.2, 127.0, 55.1, 29.9 |
In chloroform; at 0℃; for 1.16667h;Heating / reflux; | Thiophene-2-sulfonyl chloride (15 g, 0.082 mol) was dissolved in CHC13 (200 mL) under N2 atmosphere and then cooled to 0C. TERT-BUTYLAMINE (25.9 mL, 0.246 mol) dissolved in CHC13 (50 ML) was then added dropwise to the reaction mixture. The reaction mixture was stirred for 1 hour at room temperature and then at reflux for 10 min. Toluene (700 mL) was added and the organic phase was washed with water (3 x 50 mL), dried, and concentrated in vacuo. The sub-title product was used without further purification in the next step. 1H NMR No.(CDCL3) : 7.60 (1H, dd, J= 1.3, 3.8 Hz), 7.53 (1H, dd, J= 1.3, 5.0 Hz), 7.02 (1H, dd, J = 5.0, 3.8 Hz), 5. 13- (1 H, m), 1.24 (9H, m) 13C NMR 6 (CDC13) : 145.0, 131.7, 131.2, 127.0, 55.1, 29.9 | |
In chloroform; at 20℃; for 1.16667h;Heating / reflux; | Thiophene-2-sulfonyl chloride (15 g, 0.082 mol) was dissolved in CHC13 (200 mL) under N2 atmosphere and then cooled to 0C. tert-Butylamine (25.9 mL, 0.246 mol) dissolved in CHC13 (50 ML) was then added dropwise to the reaction mixture. The reaction mixture was stirred for 1 h at room temperature and then at reflux for 10 min. Toluene (700 mL) was added and the organic phase was washed with water (3 x 50 mL), dried, and concentrated IFS vacuo. The sub-title product was used without further purification in the next step. LH NMR B (CDC13) : 7.60 (1H, dd, J= 1.3, 3.8 Hz), 7.53 (1H, dd, J= 1.3, 5.0 Hz), 7.02 (1H, dd, J = 5. 0,3. 8 HZ), 5.13 (1H, m), 1.24 (9H, m) 13C NMR 8 (CDC13) : 145.0, 131.7, 131.2, 127.0, 55.1, 29.9 | |
In chloroform; at 0 - 20℃; for 1.16667h;Heating / reflux; | Thiophene-2-sulfonyl chloride (15 g, 0.082 mol) was dissolved in CHC13 (200 mL) under N2 atmosphere and then cooled to 0oC. tert-Butylamine (25.9 ML9 0.246 mol) dissolved in CHC13 (50 mL) was then added dropwise to the reaction mixture. The reaction mixture was stirred for 1 h at room temperature and then at reflux for 10 min. Toluene (700 mL) was added and the organic phase was washed with water (3 x 50 mL), dried, and concentrated in vacuo. The sub-title product was used without further purification in the next step. 'H NMR (CDC13) 8 7.60 (1H, dd, J=1.3, 3.8 Hz), 7.53 (1H, dd, J=1.3, 5.0 Hz), 7.02 (1H, dd, J=5.0, 3. 8 Hz), 5.13 (1H, m), 1.24 (9H, M) 13C NMR (CDC13) 5 145.0, 131.7, 131.2, 127.0, 55.1, 29.9 | |
In chloroform; at 0 - 20℃; for 1.16667h;Heating / reflux; | (a) LambdaLfe7Y-Butylthiophene-2-sulfonamide; Thiophene-2-sulfonyl chloride (15 g, 0.082 mol) was dissolved in CHCl3 (200 mL) under N2 atmosphere and then cooled to 00C. tert-Butylamine (25.9 mL, 0.246 mol) dissolved in CHCl3 (50 mL) was then added' drop wise to the reaction mixture. The reaction mixture was stirred for 1 h at room temperature and then at reflux for 10 min. Toluene (700 mL) was added and the organic phase was washed with water (3 x 50 mL), dried, and concentrated in vacuo. The sub-title product was used without further purification in the next step.1H NMR delta (CDCl3): 7.60 (IH, dd, J=1.3, 3.8 Hz), 7.53 (IH, dd5 J=I .3, 5.0 Hz), 7.02 (IH, dd, J=5.0, 3.8 Hz), 5.13(1H, m), 1.24 (9H5 m). 13C NMR delta (CDCl3): 145.0, 131.7, 131.2, 127.0, 55.1, 29.9. | |
In chloroform; at 0 - 20℃; for 1.16667h;Heating / reflux; | (a) N-fe7f-Butylthiopliene-2-sulfonamide;Thiophene-2-sulfonyl chloride (15 g, 0.082 mol) was dissolved in CHCl3 (200 mL) under N2 atmosphere and then cooled to 0C. fez-f-Butylamine (25.9 mL, 0.246 mol) dissolved in CHCl3 (50 mL) was then added dropwise to the reaction mixture. The reaction mixture was stirred for 1 h at room temperature and then at reflux for 10 min. Toluene (700 mL) was added and the organic phase was washed with water (3 x 50 mL), dried, and concentrated in vacuo. The sub-title product was used without further purification in the next step. 1H NMR (CDCl3) delta 7.60 (IH, dd, J=1.3, 3.8 Hz), 7.53 (IH, dd, J=1.3, 5.0 Hz), 7.02 (IH, dd, J=5.0, 3.8 Hz), 5.13 (IH, m), 1.24 (9H, m). 13C NMR (CDCl3) delta 145.0, 131.7, 131.2, 127.0, 55.1, 29.9. | |
In chloroform; at 0 - 20℃; for 1.16667h;Heating / reflux; | (a) iV-fert-Butylthiophene-2-sulfonamide; Thiophene-2-sulfonyl chloride (15 g, 0.082 mol) was dissolved in CHCl3 (200 mL) under N2 atmosphere and then cooled to 0C. fe/Y-Butylamine (25.9 mL, 0.246 mol) dissolved in CHCl3 (50 mL) was then added dropwise to the reaction mixture. The reaction mixture was stirred for 1 h at room temperature and then at reflux for 10 min. Toluene (700 mL) was added and the organic phase was washed with water (3 x 50 mL), dried, and concentrated in vacuo. The sub-title product was used without further purification in the next step.1H NMR delta (CDCl3): 7.60 (IH, dd, J=I .3, 3.8 Hz)5 7.53 (IH, dd, J=1.3, 5.0 Hz), 7.02 (IH5 dd, J=5.0, 3.8 Hz)5 5.13(1H, m), 1.24 (9H5 m). 13C NMR delta (CDCl3): 145.0, 131.7, 131.2, 127.0, 55.1, 29.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium carbonate; In water; | Step A. N-(2-Thiophene-sulfonyl)-azetidine-2(S)-carboxylic Acid To a magnetically stirred mixture of azetidine-2(S)-carboxylic acid (1.0 g, 10 mmol) and Na2CO3 (2.1 g, 20 mmol) in 30 mL of water at 0 C. was added thiophene-2-sulfonyl chloride (1.8 g, 10 mmol), and the reaction was allowed to slowly warm up to room temperature overnight. The reaction was quenched by careful addition of concentrated HCl at 0 C. to pH above 2, and the product was extracted with EtOAc (3*15 mL). The extracts were dried over Na2SO4, and concentrated to dryness to provide the title compound as a white solid, which is >90% pure by 1H-NMR and used without further purification. 400 MHz 1H NMR (CD3OD): delta 2.2-2.4 (m, 2H), 3.7-3.9 (m, 2H), 4.42 (dd, 1H), 7.30 (dd, 1H), 7.75 (dd, 1H), 7.95 (dd, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; | Example 142 3-(Thiophene-2-sulfonylamino)-4-methoxy-N-phenyl-benzamide Prepared according to the procedure described for Example 121 using 2-thiophenesulfonyl chloride (1.82 g, 10 mmol), 3-amino-4-methoxy-N-phenyl-benzamide (2.43 g, 10 mmol), and pyridine (25 mL) to afford the product (3.457 g); m.p. 180-183 C. after trituration in hexanes/ethyl acetate (1:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium carbonate; In dichloromethane; at 0 - 20℃; | General procedure: To a stirred solution of <strong>[56293-29-9]aloperine</strong> (2.0 mmol) and K2CO3(6.0 mmol) in dichloromethane (20 mL), and the substituted benzoylchloride or sulfonyl chloride (2.0 mmol) was added. The reactionmixture was stirred at 0 C for 1e2 h until TLC analysisshowed completion of the reaction. Then the solvent was washedsuccessively with water (20 mL), brine (20 mL). The organic layerwas concentrated and purified by flash column chromatography onsilica gel with CH2Cl2/CH3OH as the eluent to get target compounds3aeb or 4aee. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.1% | With triethylamine; In dichloromethane; at 25℃; for 4h; | General procedure: To a mechanically stirred suspension of suspension of 1 (0.21 g, 0.53 mmol) in 30 ml CH2Cl2 were added triethylamine (0.5 ml) and aromatic sulfonyl chloride (0.53 mmol) at 25 C for 4 h. The reaction process was detected by TLC method. Then, antagonized by dilute sodium hydroxide, extracted, and washed with ether and water, evaporated under vacuum. Finally, the mixture was recrys-tallizated from ethyl acetate , providing a total product yield of 65.4%-88.6 %.2-(11-Chlorobenzofuro[3,2-b]quinolin-7-yloxy)-N,N-dimethy-lethanamine (2): Yellow solid; yield 0.2 g, 77.1 %; m. p. 218-219 C; 1 H NMR (400 MHz, DMSO-d6): δ 11.85 (s, 1H), 8.05 (d, J = 6.1 Hz, 1H), 7.82 (d, J = 8.9 Hz, 2H), 7.69 (d, J = 5.0 Hz, 1H), 7.09 - 7.04 (m, 1H), 6.99 (d, J = 8.9 Hz, 2H), 6.24 (s, 1H), 3.84 (s, 3H), 2.82 (t, J = 6.7 Hz, 2H), 1.85 (t, J = 6.6 Hz, 2H), 1.34 (s, 6H); APCI-MS m/z: 513 [M + H] + ; Anal. calcd. for C25H22O8S2. 2H2O: C, 58.36; H, 4.31. Found: C, 58.37; H, 4.32. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.04% | With dmap; N-ethyl-N,N-diisopropylamine; In acetonitrile; at 0 - 5℃; for 2h; | Add III-3 (0.80g, 5.03mmol), DMAP (129mg, 1.06mmol), DIEA (2.50mL, 15.08mmol) to 100mL three-necked flask, stir and dissolve with 10mL acetonitrile, slowly add at 05C Thiazol-2-sulfonyl chloride (IV-2, 1.10g, 6.04mmol) in 10mL acetonitrile solution, after the addition is completed, stirring is continued for 2 hours under low temperature conditions.TLC monitoring of raw material reactionsCompletely, concentrate the reaction solution, dissolve it with 30 mL of ethyl acetate, wash with 40 mL of water, and extract twice with ethyl acetate (20 mL×2)The organic phase is washed with a saturated sodium chloride solution and dried over anhydrous sodium sulfate; filtered, filtered, and then filtered and evaporated.After drying, 1.46gBrownish yellow solidV-3,The yield was 76.04%. |
A683360 [2766-74-7]
5-Chlorothiophene-2-sulfonyl chloride
Similarity: 0.80
A683360 [2766-74-7]
5-Chlorothiophene-2-sulfonyl chloride
Similarity: 0.80