3-oxa-8-azabicyclo[3.2.1]octane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2,4-dibromothiazole (0.585 g, 2.41 mmol) in DMF (10 ml) were added 3-oxa-8-azabicyclo[3.2.1]octane (prepared according to the procedure given in WO 2010/120854, 0.3 g, 2.65 mmol) and DIPEA (0.47 gm, 0.63 ml, 3.62 mmol) under a stream of nitrogen. The reaction mixture was then stirred at 80° C. for 18 hrs and the progress of reaction was monitored by TLC. The reaction mixture was cooled to room temperature; quenched with cold water (20 ml) and extracted with ethyl acetate (3×30 ml). The combined organic layer was washed with water (2×10 ml), dried over sodium sulphate and concentrated to give crude compound; which was purified by flash column chromatography using 20% ethyl acetate in hexanes as an eluent to obtain the title compound (0.31 g, 46.7%). MS: m/z 276 (M+1). prepared the progress of reaction The reaction mixture was cooled to room temperature quenched with cold water (20 ml) extracted with ethyl acetate (3×30 ml) The combined organic layer was washed with water (2×10 ml) dried over sodium sulphate concentrated to give crude compound which was purified by flash column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2,4-dibromothiazole (0.585 g, 2.41 mmol) in DMF (10 ml) were added 3-oxa-8-azabicyclo[3.2.1]octane (prepared according to the procedure given in WO 2010/120854, 0.3 g, 2.65 mmol) and DIPEA (0.47 gm, 0.63 ml, 3.62 mmol) under a stream of nitrogen. The reaction mixture was then stirred at 80° C. for 18 hrs and the progress of reaction was monitored by TLC. The reaction mixture was cooled to room temperature; quenched with cold water (20 ml) and extracted with ethyl acetate (3×30 ml). The combined organic layer was washed with water (2×10 ml), dried over sodium sulphate and concentrated to give crude compound; which was purified by flash column chromatography using 20% ethyl acetate in hexanes as an eluent to obtain the title compound (0.31 g, 46.7%). MS: m/z 276 (M+1). prepared the progress of reaction The reaction mixture was cooled to room temperature quenched with cold water (20 ml) extracted with ethyl acetate (3×30 ml) The combined organic layer was washed with water (2×10 ml) dried over sodium sulphate concentrated to give crude compound which was purified by flash column chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromothiazole-2-carboxylic acid (prepared according to the procedure given in WO 2008/57336, 1.4 g, 6.73 mmol) in DMF (15 ml) was added HOBT (1.13 g, 7.40 mmol) at room temperature, followed by the addition of 3-oxa-8-azabicyclo[3.2.1]octane (prepared according to the procedure given in WO 2010/120854, 0.76 g, 6.69 mmol). Reaction mixture was cooled to 0° C. and to this were added EDC (1.93 g, 10.10 mmol) and triethylamine (3.40 g, 4.69 ml, 33.60 mmol). Reaction mixture was stirred at room temperature for 15 hr. The progress of reaction was monitored by TLC. The reaction mixture was concentrated under reduced pressure. The residue so obtained was taken in ethyl acetate (150 ml) and washed with saturated sodium bicarbonate solution (1×40 ml), brine (1×20 ml). The organic layers separated were dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to get a crude product. This crude product was purified by column chromatography over silica gel (100-200 mesh) using 2.5% methanol in DCM as an eluent to obtain the title compound (0.35 g. 17.15%). MS: m/z 304 (M+1). prepared Reaction mixture Reaction mixture The progress of reaction The reaction mixture was concentrated under reduced pressure The residue so obtained washed with saturated sodium bicarbonate solution (1×40 ml), brine (1×20 ml) The organic layers separated were dried over anhydrous sodium sulphate filtered concentrated under reduced pressure to get a crude product This crude product was purified by column chromatography over silica gel (100-200 mesh)

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

Procedure: The title compound (54 mg, colorless oil) was prepared from 1-(4-bromophenyl)propan-2-one (130 mg) and 3-oxa-8-azabicyclo[3.2.1]octane (100 mg), as in Reference Example P-R5-1.