2-bromo-4-fluorobenzenesulfonyl chloride

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

実験手順: Prepared by proceeding in a similar manner to Intermediate 18, starting from methyl (1aRS,7bSR)-5-amino-1,1-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 61) and 2-bromo-4-fluorobenzene sulfonyl chloride, as a colourless foam. Prepared

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

実験手順: Prepared by proceeding in a similar manner to Intermediate 18, starting from methyl (1aRS,7bSR)-5-amino-1,1-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 61) and 2-bromo-4-fluorobenzene sulfonyl chloride, as a colourless foam. Prepared

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

実験手順: Prepared by proceeding in a similar manner to Intermediate 41, starting from methyl (1aRS,7bSR)-5-amino-7b-methyl-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 50) and 2-bromo-4-fluorobenzenesulfonyl chloride. Prepared

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

実験手順: Prepared by proceeding in a similar manner to Intermediate 41, starting from methyl (1aRS,7bSR)-5-amino-7b-methyl-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 50) and 2-bromo-4-fluorobenzenesulfonyl chloride. Prepared

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

実験手順: Methyl (1aRS,7bSR)-5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 42, 0.120 g) was suspended in DCM (5 mL). Pyridine (0.885 mL) and 2-bromo-4-fluorobenzenesulfonyl chloride (0.180 g) were added. The mixture was stirred at room temperature for 5 hours then concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with 0.5M aqueous hydrochloric acid solution, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-10% to give methyl (1aRS,7bSR)-5-(2-bromo-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.208 g) as a colourless oil. then concentrated in vacuo The residue was dissolved in ethyl acetate washed with 0.5M aqueous hydrochloric acid solution dried (MgSO4) filtered The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-10%

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

実験手順: Methyl (1aRS,7bSR)-5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 42, 0.120 g) was suspended in DCM (5 mL). Pyridine (0.885 mL) and 2-bromo-4-fluorobenzenesulfonyl chloride (0.180 g) were added. The mixture was stirred at room temperature for 5 hours then concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with 0.5M aqueous hydrochloric acid solution, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-10% to give methyl (1aRS,7bSR)-5-(2-bromo-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.208 g) as a colourless oil. then concentrated in vacuo The residue was dissolved in ethyl acetate washed with 0.5M aqueous hydrochloric acid solution dried (MgSO4) filtered The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-10%

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

実験手順: Prepared by proceeding in a similar manner to Intermediate 18, starting from methyl cis-(3aRS,9bRS)-5-acetyl-7-amino-1,2,3a,4,5,9b-hexahydrofuro[2,3-c]quinoline-6-carboxylate (Intermediate 29) and 2-bromo-4-fluorobenzenesulfonyl chloride. Prepared

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

実験手順: Prepared by proceeding in a similar manner to Intermediate 18, starting from methyl 7-amino-1,2-dihydrofuro[2,3-c]quinoline-6-carboxylate (Intermediate 23) and 2-bromo-4-fluorobenzenesulfonyl chloride and stirring at room temperature for 3 days. Prepared

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

実験手順: 2-Bromo-4-fluorobenzenesulfonyl chloride (0.335 g) was added to a solution of methyl cis-(3aRS,9bRS)-7-amino-1,3a,4,9b-tetrahydro-2H-furo[2,3-c]chromene-6-carboxylate (Intermediate 19, 0.255 g) in DCM (4 mL) and pyridine (2 mL) and the resultant mixture was stirred at room temperature overnight. The mixture was evaporated to dryness and the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100% to give methyl cis-(3aRS,9bRS)-7-(2-bromo-4-fluorobenzenesulfonylamino)-1,3a,4,9b-tetrahydro-2H-furo[2,3-c]chromene-6-carboxylate (0.486 g) as a yellow gum. The mixture was evaporated to dryness the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100%

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

実験手順: 2-Bromo-4-fluorobenzenesulfonyl chloride (0.335 g) was added to a solution of methyl cis-(3aRS,9bRS)-7-amino-1,3a,4,9b-tetrahydro-2H-furo[2,3-c]chromene-6-carboxylate (Intermediate 19, 0.255 g) in DCM (4 mL) and pyridine (2 mL) and the resultant mixture was stirred at room temperature overnight. The mixture was evaporated to dryness and the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100% to give methyl cis-(3aRS,9bRS)-7-(2-bromo-4-fluorobenzenesulfonylamino)-1,3a,4,9b-tetrahydro-2H-furo[2,3-c]chromene-6-carboxylate (0.486 g) as a yellow gum. The mixture was evaporated to dryness the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100%

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

実験手順: 2-Bromo-4-fluorobenzenesulfonyl chloride (0.410 g) was added to a solution of methyl 6-amino-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-5-carboxylate (Intermediate 55, 0.290 g) in pyridine (10 mL) and DCM (10 mL) and the resultant mixture was stirred at room temperature for 24 hours. The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was separated, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-15% to give a sandy coloured solid which was triturated with ether and filtered to give methyl 6-(2-bromo-4-fluorobenzenesulfonylamino)-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-5-carboxylate (0.268 g). The mixture was concentrated in vacuo the residue was partitioned between ethyl acetate and water The organic layer was separated dried (Na2SO4) filtered The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of methanol and DCM with a gradient of 0-15% to give a sandy coloured solid which was triturated with ether filtered

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

実験手順: 2-Bromo-4-fluorobenzenesulfonyl chloride (0.091 g) was added to a solution of tert-butyl (R)-6-amino-1,2,2a,3-tetrahydro-4-oxa-8b-azacyclobuta[a]naphthalene-5-carboxylate (Intermediate 44, 0.092 g) in pyridine (2 mL) and DCM (2 mL) and the mixture was stirred at room temperature for 1 hour. The mixture was concentrated in vacuo and the residue was partitioned between DCM and 1M hydrochloric acid and filtered through a phase separator. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25% to give tert-butyl (R)-6-(2-bromo-4-fluorobenzenesulfonylamino)-1,2,2a,3-tetrahydro-4-oxa-8b-azacyclobuta-[a]naphthalene-5-carboxylate (0.062 g). The mixture was concentrated in vacuo the residue was partitioned between DCM and 1M hydrochloric acid filtered through a phase separator The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25%