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1.H Benzo[b]thiophene-2-carboxamide, 6-methoxy-3-(1-methylethoxy)-N- 1H-tetrazol-5-yl
EXAMPLE 1(H) Benzo[b]thiophene-2-carboxamide, 6-methoxy-3-(1-methylethoxy)-N- 1H-tetrazol-5-yl A mixture of benzo[b]thiophene-2-carboxylic acid-6-methoxy-3(1-methylethoxy) (10.41 g, 0.039 mole) and 1,1'-carbonyldiimidazole (7.61 g, 0.047 mole) in acetonitrile (200 ml) is refluxed with stirring under nitrogen for 80 minutes. A solution of 5-aminotetrazole (3.99 g, 0.047 mole) and triethylamine (4.75 g, 0.047 mole) in acetonitrile (100 ml) is added dropwise. The mixture is heated at reflux for 21.5 hours, then most of the acetonitrile is removed under water aspirator pressure at 40°. The residue is treated with cold water (~700 ml) then acidified with acetic acid (14.5 g). The resulting solid is separated by filtration, washed with water, then with ether, and dried to give 12.1 g of a solid. Recrystallization from methanol gives 11.06 g (84.9%) of analytically pure product, mp 237°-9° C. (dec).
6.H Benzo[b]thiophene-2-carboxamide, 3-(1-methylethoxy)-5-methyl-N-1H-tetrazol-5-yl
EXAMPLE 6(H) Benzo[b]thiophene-2-carboxamide, 3-(1-methylethoxy)-5-methyl-N-1H-tetrazol-5-yl A mixture of benzo[b]thiophene-2-carboxylic acid-5-methyl-3(1-methylethoxy) (8.5 g, 0.034 mole), 1,1'-carbonyldiimidazole (6.62 g, 0.041 mole), 5-aminotetrazole (3.47 g, 0.041 mole), and triethylamine (4.13 g, 0.041 mole) in acetonitrile (300 ml) is treated according to the procedure in Example 1(H). There is obtained 10.32 g of the product, mp 247°-9° C. (dec). Recrystallization from methanol gives 8.17 g (80.8%) of analytically pure product, mp 247°-9° C. (dec).
7.B Benzo[b]thiophene-2-carboxamide, 6-chloro-3(1-methyl-ethoxy)-N-1H-tetrazol-5-yl
EXAMPLE 7(B) Benzo[b]thiophene-2-carboxamide, 6-chloro-3(1-methyl-ethoxy)-N-1H-tetrazol-5-yl A mixture of benzo[b]thiophene-2-carboxylic acid-6-chloro-3-(1-methylethoxy) (8.05 g, 0.03 mole) 1,1'-carbonyldiimidazole (5.79 g, 0.036 mole), 5-aminotetrazole (3.04 g, 0.036 mole) and triethylamine (3.61 g, 0.036 mole) in acetonitrile (200 ml) is treated according to the procedure in Example 1(H). There is obtained 9.8 g of the product, mp 250°-1° C. (dec). Recrystallization from dimethylformamidemethanol gives 8.4 g (84%) of analytically pure product, mp 249°-251° C. (dec).
The following are non-limiting examples of other analogs prepared by the procedures described herein above. ... Naphthylene-1-carboxylic acid {1-[(2-ethoxy-5-oxo-tetrahydrofuran-3-yl-carbamoyl)methyl]-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl}-amide; Benzo[b]thiophene-2-carboxylic {1-[(2-hydroxy-5-oxo-tetrahydrofuran-3-yl-carbamoyl)methyl]-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl}-amide; Benzo[b]thiophene-2-carboxylic {1-[(2-ethoxy-5-oxo-tetrahydrofuran-3-yl-carbamoyl)methyl]-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl}-amide; 3-Fluoro-N-{1-[(2-hydroxy-5-oxo-tetrahydrofuran-3-ylcarbamoyl)methyl]-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl}-benzamide; ...
The following are non-limiting examples of other analogs prepared by the procedures described herein above. ... Naphthylene-1-carboxylic acid {1-[(2-hydroxy-5-oxo-tetrahydrofuran-3-yl-carbamoyl)methyl]-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl}-amide; Naphthylene-1-carboxylic acid {1-[(2-ethoxy-5-oxo-tetrahydrofuran-3-yl-carbamoyl)methyl]-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl}-amide; Benzo[b]thiophene-2-carboxylic {1-[(2-hydroxy-5-oxo-tetrahydrofuran-3-yl-carbamoyl)methyl]-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl}-amide; Benzo[b]thiophene-2-carboxylic {1-[(2-ethoxy-5-oxo-tetrahydrofuran-3-yl-carbamoyl)methyl]-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl}-amide; ...
6
[ 1136-76-1 ]
[ 6314-42-7 ]
C20H16N4O2S[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
32%
With diphenylphosphoranyl azide; N-ethyl-N,N-diisopropylamine In benzene at 85℃; for 3h;
With magnesium(II) nitrate hexahydrate; urea In octane at 120℃; for 24h;
36%
Stage #1: benzo[b]thiophene-2-carboxylic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide at 25℃; for 0.0833333h;
Stage #2: With ammonium hydroxide In N,N-dimethyl-formamide at 25℃; for 0.5h;
Multi-step reaction with 2 steps
1: thionyl chloride / benzene / 2.5 h / Heating
2: NH3 / dioxane / 2 h / Ambient temperature
Multi-step reaction with 2 steps
1: thionyl chloride / toluene / 2 h / Reflux
2: ammonium hydroxide / water; dichloromethane / 1 h / 0 - 20 °C
EXAMPLE 14(B) Benzo[ b]thiophene, 2-carbonitrile-3-(1-methylethoxy) A mixture of benzo[b]thiophene-2-carboxamide, 3-(1-methylethoxy)(5.95 g, 0.025 mole), 1,1'-carbonyldiimidazole (8.2 g, 0.051 mole) and allyl bromide (24.5 g, 0.2 mole) is treated according to the procedure of Example 13B. There is obtained 5.6 g of oily residue, which is dissolved in hexane and chromatographed on silica gel (120 g). Eluding with methylene chloride gives 5.45 g (99.3%) of benzo[b]thiophene-2-carbonitrile, 3-(1-methylethoxy)-; as an oil, which is used directly in the next stage.
13.B Benzo[b]thiophene-2-carbonitrile, 5-methoxy-3-(1-methylethoxy)-
EXAMPLE 13 (B) Benzo[b]thiophene-2-carbonitrile, 5-methoxy-3-(1-methylethoxy)- A mixture of benzo[b]thiophene-2-carboxamide, 5-methoxy-3-(1-methylethoxy) (3.25 g, 0.12 mole) and 1,1'-carbonyldiimidazole (3.96 g, 0.024 mole) in acetonitrile (220 ml) is stirred at room temperature for 80 minutes. Allylbromide (11.8 g, 0.098 mole) is added and the reaction mixture is heated at reflux for 12 hours. Most of the volatiles are removed under reduced pressure and the residue obtained is dissolved in ether and washed successively with dilute hydrochloric acid, water, aqueous sodium bicarbonate and water. The extract is dried over sodium sulfate and the solvent is removed to give 3.2 g of oily residue. The oil is purified by chromatography on silica gel (110 g). Eluding with methylene chloride gives 3.01 g (100%) of a solid, mp 80°-1° C. Recrystallization from hexane gives 2.77 g (92%) of analytically pure benzo[b]thiophene-2-carbonitrile, 5-methoxy-3-(1-methylethoxy); mp 80°-1° C.
15.F Benzo[b]thiophene-2-carboxamide, 5-methoxy-3-[(1-methylethyl) thio-N-1H-tetrazol-5-yl]
EXAMPLE 15(F) Benzo[b]thiophene-2-carboxamide, 5-methoxy-3-[(1-methylethyl) thio-N-1H-tetrazol-5-yl] A mixture of benzo[b]thiophene-2-carboxylic acid, 5-methoxy-3-[(1-methylethyl)thio]- (2.5 g, 0.0085 mole) and 1,1'-carbonyldiimidazole (1.72 g, 0.011 mole) in acetonitrile (150 ml) is refluxed with stirring under nitrogen for 100 minutes. A solution of 5-aminotetrazole (0.9 g, 0.011 mole) and triethylamine (1.07 g, 0.011 mole) in acetonitrile (100 ml) is added dropwise. The mixture is heated at reflux for 17 hours, then most of the acetonitrile is removed under water aspirator pressure at 40° C. The residue is treated with cold water (~500 ml), acidified with acetic acid (3.4 ml) and stirred. The resulting solid is separated by filtration, washed with water, then with ether and dried to give 2.4 g of a solid. Recrystallization from methanol gives 1.7 g (55%) of analytically pure benzo[b]thiophene-2-carboxamide, 5-methoxy-3-[(1methylethyl)thio-N- 1H-tetrazol-5-yl]-; mp 236° C. (dec).
R.44 Reference Example 44
Reference Example 44 In substantially the same manner as in Reference Example 31, 2-benzo[b]thiophenecarboxamide was allowed to react with 1,3-dichloroacetone to give 2-(2-benzo[b]thienyl)-4-chloromethyloxazole. The yield was 33%. Recrystallization from ethyl acetate-hexane gave colorless prisms, mp 150-151° C.
With acetic acid; isopentyl nitrite at 80℃; for 24h; Inert atmosphere;
Benzo[b]thiophene-2-carboxylic acid (15)
Benzo[b]thiophene-2-carboxamide (0.1772 g, 1 mmol)was dissolved in acetic acid (2 mL), and to the stirring solution was added amyl nitrite (0.40 mL, 3mmol). The reaction was placed under N2 atmosphere and heated to 80 °C for 24 hours, whereupon thereaction was complete by consumption of starting material by TLC. The solution was condensed andco-evaporated with toluene (2 x 5 mL), then purified via recrystallization from acetone. The resultingsuspension was filtered to afford off-white powder (0.0846 g, 0.47 mmol)
3,4-diethylbenzo[4,5]thieno[2,3-c]pyridin-1(2H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With potassium hexafluorophosphate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; copper diacetate; sodium acetate In toluene at 120℃; for 24h; regioselective reaction;
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