2-iodoethoxybenzene

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4,6,6a,8,9,10a-hexahydro-10a-methyl-7H-indolo[3,4-gh][1.4]benzoxazine (85 mg, 0.37 mmol) in DMF (5 ml) were added potassium carbonate (255 mg, 1.9 mmol) and 1-iodo-2-phenoxyethane (99 mg, 0.4 mmol). The mixture was heated at 60° C for 24 hours. After completion of the reaction, the reaction mixture was added to a mixture of ice water and ethyl acetate. The organic layer was separated, washed with a saturated aqueous saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to a silica gel column chromatography, eluting with n-hexane-ethyl acetate (2:1), to afford 59 mg (46%) of the title compound as an amorphous crystalline product. After completion of the reaction The organic layer was separated washed with a saturated aqueous saline solution dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure eluting with n-hexane-ethyl acetate (2:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4,6,6a,8,9,10a-hexahydro-10a-methyl-7H-indolo[3,4-gh][1.4]benzoxazine (85 mg, 0.37 mmol) in DMF (5 ml) were added potassium carbonate (255 mg, 1.9 mmol) and 1-iodo-2-phenoxyethane (99 mg, 0.4 mmol). The mixture was heated at 60° C for 24 hours. After completion of the reaction, the reaction mixture was added to a mixture of ice water and ethyl acetate. The organic layer was separated, washed with a saturated aqueous saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to a silica gel column chromatography, eluting with n-hexane-ethyl acetate (2:1), to afford 59 mg (46%) of the title compound as an amorphous crystalline product. After completion of the reaction The organic layer was separated washed with a saturated aqueous saline solution dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure eluting with n-hexane-ethyl acetate (2:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-hydroxy-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one O-tert-butyl-oxime (example 81A) (150 mg, 0.43 mmol), cesium carbonate (280 mg, 0.85 mmol) and (2-Iodo-ethoxy)-benzene (413 mg, 3.87 mmol), in dimethylformamide (6 rill) was stirring at room temperature for 24 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were washed with a saturated solution of ammonium chloride, water, brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography over silica gel (gradient cyclohexane/ethyl acetate: 0-10%) to yield the title compound (77 mg, 38%) as a yellow solid. extracted with ethyl acetate The organic layers were washed with a saturated solution of ammonium chloride, water, brine dried over sodium sulfate filtered concentrated The residue was purified by flash chromatography over silica gel (gradient cyclohexane/ethyl acetate: 0-10%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 0.20 g (0.8 mmole) of 2-chloro-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-292) in 2 mL of dimethylformamide was added 0.53 g (1.6 mmole) of cesium carbonate, followed by 0.8 g (3.2 mole) of (2-iodo-ethoxy)-benzene. After stirring at 50 degrees overnight, the mixture was filtered and then concentrated under reduced pressure. Dichloromethane and saturated sodium carbonate were added. The mixture was extracted twice with dichloromethane. The combined organic layers were washed three times with sodium carbonate, three times with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 0.28 g of 2-chloro-7,7-difluoro-5-methyl-9-(2-phenoxy-ethyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-304) as an oil. the mixture was filtered concentrated under reduced pressure Dichloromethane and saturated sodium carbonate were added The mixture was extracted twice with dichloromethane The combined organic layers were washed three times with sodium carbonate, three times with water dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4,6,6a,8,9,10a-hexahydro-10a-methyl-7H-indolo[3,4-gh][1.4]benzoxazine (85 mg, 0.37 mmol) in DMF (5 ml) were added potassium carbonate (255 mg, 1.9 mmol) and 1-iodo-2-phenoxyethane (99 mg, 0.4 mmol). The mixture was heated at 60° C for 24 hours. After completion of the reaction, the reaction mixture was added to a mixture of ice water and ethyl acetate. The organic layer was separated, washed with a saturated aqueous saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to a silica gel column chromatography, eluting with n-hexane-ethyl acetate (2:1), to afford 59 mg (46%) of the title compound as an amorphous crystalline product. After completion of the reaction The organic layer was separated washed with a saturated aqueous saline solution dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure eluting with n-hexane-ethyl acetate (2:1)