1-(dimethoxymethyl)azepane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 1.2 g (5 mmoles) of 6-amino-2,2-dimethyl-3-(5-tetrazolyl)penam, 1.0 g (10 mmole) of triethylamine and 30 ml of dichloromethane, cooled to 0° C., is added 0.54 g (5 mmole) of chlorotrimethylsilane. After 15 minutes, 0.86 (5 mmole) of 1-(dimethoxymethyl)hexahydroazepine (British Patent No. 1,293,590) is added, and stirring is continued for a further 1 hour. The volatile components are removed by evaporation in vacuo, and then the residue is extracted with 25 ml of acetone. The insoluble material is filtered off, and the acetone is evaporated in vacuo to a yellow foam, which changes to a white powder on trituration with ether. This affords 1.44 g (82% yield) of 6-([hexahydro-1-azepinyl]methyleneamino)-2,2-dimethyl-3-(5-tetrazolyl)penam. The infrared spectrum of the product (KBr disc) shows absorption bands at 1795 cm-1 (β-lactam), 1706 cm-1 and 1645 cm-1. The NMR spectrum (CDCl3) shows absorption bands at 8.00 ppm (singlet, 1H, N--CH=N), 5.90 and 5.60 ppm (two doublets, 2H, J = 4 Hz, C-5 and C-6 hydrogens), 5.40 ppm (singlet, 1H, C-3 hydrogen), 3.90-3.50 (multiplet, 4H, CH2 --N--CH2), 2.00-1.50 ppm (multiplet, 11H, C-2 methyl hydrogens and [CH2 ]4) and 1.20 ppm (singlet, 3H, C-2 methyl hydrogens). Examination of the product by thin-layer chromatography (0.2M NaOAc: acetone; 1:6) showed a single spot (Rf 0.23). is continued for a further 1 hour The volatile components are removed by evaporation in vacuo the residue is extracted with 25 ml of acetone The insoluble material is filtered off the acetone is evaporated in vacuo to a yellow foam, which

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 1.2 g (5 mmoles) of 6-amino-2,2-dimethyl-3-(5-tetrazolyl)penam, 1.0 g (10 mmole) of triethylamine and 30 ml of dichloromethane, cooled to 0° C., is added 0.54 g (5 mmole) of chlorotrimethylsilane. After 15 minutes, 0.86 (5 mmole) of 1-(dimethoxymethyl)hexahydroazepine (British Patent No. 1,293,590) is added, and stirring is continued for a further 1 hour. The volatile components are removed by evaporation in vacuo, and then the residue is extracted with 25 ml of acetone. The insoluble material is filtered off, and the acetone is evaporated in vacuo to a yellow foam, which changes to a white powder on trituration with ether. This affords 1.44 g (82% yield) of 6-([hexahydro-1-azepinyl]methyleneamino)-2,2-dimethyl-3-(5-tetrazolyl)penam. The infrared spectrum of the product (KBr disc) shows absorption bands at 1795 cm-1 (β-lactam), 1706 cm-1 and 1645 cm-1. The NMR spectrum (CDCl3) shows absorption bands at 8.00 ppm (singlet, 1H, N--CH=N), 5.90 and 5.60 ppm (two doublets, 2H, J = 4 Hz, C-5 and C-6 hydrogens), 5.40 ppm (singlet, 1H, C-3 hydrogen), 3.90-3.50 (multiplet, 4H, CH2 --N--CH2), 2.00-1.50 ppm (multiplet, 11H, C-2 methyl hydrogens and [CH2 ]4) and 1.20 ppm (singlet, 3H, C-2 methyl hydrogens). Examination of the product by thin-layer chromatography (0.2M NaOAc: acetone; 1:6) showed a single spot (Rf 0.23). is continued for a further 1 hour The volatile components are removed by evaporation in vacuo the residue is extracted with 25 ml of acetone The insoluble material is filtered off the acetone is evaporated in vacuo to a yellow foam, which

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of t-butyl 3-acetoxymethyl-7-(5-aminomethylbenzimidazol-2-yl)aminoceph-3-em-4-carboxylate (93 mg.) in dioxane (2 ml.) and methanol (3 ml.) at 20° was added dimethoxyhexahydro-1H-azepin-1-ylmethane (30 mg.) and then triethylamine. The mixture was cooled to 0° and stirred for 30 minutes. Two equivalents of HBr in methanol were added and the solvent evaporated. The residue was dissolved in the minimum CH2Cl2 and triethylamine hydrobromide precipitated by addition of ether. The product was purified by chromatography on magnesium silicate using CH2Cl2 /MeOH 98:2 v/v as eluant to give t-butyl 3-acetoxymethyl-7-(5-hexahydro-1H-azepin-1-ylmethyleneaminomethylbenzimidazol-2-yl)aminoceph-3-em-4-carboxylate having the following n.m.r. in d6DMSO: 1.63 (s, 9H); 1.7 (s, 8H); 2.17 (s, 3H); 3.3-4.0 (br, 6H); 4.67 (s, 2H); 4.75 (d, 1H); 5.1 (d, 1H); 5.38 (d, 1H); 6.0 (d, 1H); 6.8-7.5 (m, 3H); 8.43 (s, 1H). The mixture was cooled to 0° the solvent evaporated The residue was dissolved in the minimum CH2Cl2 and triethylamine hydrobromide precipitated by addition of ether The product was purified by chromatography on magnesium silicate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 1.2 g (5 mmoles) of 6-amino-2,2-dimethyl-3-(5-tetrazolyl)penam, 1.0 g (10 mmole) of triethylamine and 30 ml of dichloromethane, cooled to 0° C., is added 0.54 g (5 mmole) of chlorotrimethylsilane. After 15 minutes, 0.86 (5 mmole) of 1-(dimethoxymethyl)hexahydroazepine (British Pat. No. 1,293,590) is added, and stirring is continued for a further 1 hour. The volatile components are removed by evaporation in vacuo, and then the residue is extracted with 25 ml of acetone. The insoluble material is filtered off, and the acetone is evaporated in vacuo to a yellow foam, which changes to a white powder on trituration with ether. This affords 1.44 g (82% yield) of 6-([hexahydro-1-azepinyl]methyleneamino)-2,2-dimethyl-3-(5-tetrazolyl)penam. The infrared spectrum of the product (KBr disc) shows absorption bands at 1795 cm-1 (β-lactam), 1706 cm-1 and 1645 cm-1. The NMR spectrum (CDCl3) shows absorption bands at 8.00 ppm (singlet, 1H, N--CH=N), 5.90 and 5.60 ppm (two doublets, 2 H, J=4 Hz, C-5 and C-6 hydrogens), 5.40 ppm (singlet, 1H, C-3 hydrogen), 3.90-3.50 (multiplet, 4H, CH2 --N--CH2), 2.00-1.50 ppm (multiplet, 11H, C-2 methyl hydrogens and [CH2 ]4) and 1.20 ppm (singlet, 3H, C-2 methyl hydrogens). Examination of the product by thin-layer chromatography (0.2 M NaOAc: acetone; 1:6) showed a single spot (Rf 0.23). 1,293,590) is added is continued for a further 1 hour The volatile components are removed by evaporation in vacuo the residue is extracted with 25 ml of acetone The insoluble material is filtered off the acetone is evaporated in vacuo to a yellow foam, which

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 1.2 g (5 mmoles) of 6-amino-2,2-dimethyl-3-(5-tetrazolyl)penam, 1.0 g (10 mmole) of triethylamine and 30 ml of dichloromethane, cooled to 0° C., is added 0.54 g (5 mmole) of chlorotrimethylsilane. After 15 minutes, 0.86 (5 mmole) of 1-(dimethoxymethyl)hexahydroazepine (British Patent No. 1,293,590) is added, and stirring is continued for a further 1 hour. The volatile components are removed by evaporation in vacuo, and then the residue is extracted with 25 ml of acetone. The insoluble material is filtered off, and the acetone is evaporated in vacuo to a yellow foam, which changes to a white powder on trituration with ether. This affords 1.44 g (82% yield) of 6-([hexahydro-1-azepinyl]methyleneamino)-2,2-dimethyl-3-(5-tetrazolyl)penam. The infrared spectrum of the product (KBr disc) shows absorption bands at 1795 cm-1 (β-lactam), 1706 cm-1 and 1645 cm-1. The NMR spectrum (CDCl3) shows absorption bands at 8.00 ppm (singlet, 1H, N--CH=N), 5.90 and 5.60 ppm (two doublets, 2H, J = 4 Hz, C-5 and C-6 hydrogens), 5.40 ppm (singlet, 1H, C-3 hydrogen), 3.90-3.50 (multiplet, 4H, CH2 --N--CH2), 2.00-1.50 ppm (multiplet, 11H, C-2 methyl hydrogens and [CH2 ]4) and 1.20 ppm (singlet, 3H, C-2 methyl hydrogens). Examination of the product by thin-layer chromatography (0.2M NaOAc: acetone; 1:6) showed a single spot (Rf 0.23). is continued for a further 1 hour The volatile components are removed by evaporation in vacuo the residue is extracted with 25 ml of acetone The insoluble material is filtered off the acetone is evaporated in vacuo to a yellow foam, which