7-氟-1-甲基-1,2,3,4-四氢异喹啉

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In close analogy to the procedure described in Example 1, 6-chloro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 7-fluoro-1-methyl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In close analogy to the procedure described in Example 1, 6-chloro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 7-fluoro-1-methyl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In close analogy to the procedure described in Example 1, 6-chloro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 7-fluoro-1-methyl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In close analogy to the procedure described in Example 1, 6-chloro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 7-fluoro-1-methyl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 80 mg (0.33 mmol) of 6-Bromo-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid, 66 mg (0.40 mmol) of 7-fluoro-1-methyl-1,2,3,4-tetrahydro-isoquinoline, 63 mg (0.33 mmol) of EDC and 50 mg (0.12 mmol) of HOBt in 2 mL of DMF is stirred at room temperature for 24 h. The mixture is concentrated in vacuo and the solid residue is partitioned between methylene chloride (3 mL) and saturated aqueous sodium hydrocarbonate solution (3 mL). The organic layer is separated, washed with 0.5 N HCl, water and brine and concentrated in vacuo. The mixture is concentrated in vacuo the solid residue is partitioned between methylene chloride (3 mL) and saturated aqueous sodium hydrocarbonate solution (3 mL) The organic layer is separated washed with 0.5 N HCl, water and brine concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In close analogy to the procedure described above, 7-fluoro-1-methyl-3,4-dihydro-isoquinoline is reacted with sodium triacetoxyborohydride to provide the title compound.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In accordance with the same procedures as in Steps 1, 2, and 3 of Preparation 21, except for using 4-fluorophenethylamine and acetyl chloride, 7-fluoro-1-methyl-1,2,3,4-tetrahydroisoquinoline was obtained. In accordance with the same procedures as in Preparation 20, the titled compound was obtained as pale yellow oil. (Yield: 69%) The product was used in the subsequent step without further purification. In accordance with the same procedures as in Steps 1, 2, and 3 of Preparation 21

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In accordance with the same procedures as in Steps 1, 2, and 3 of Preparation 21, except for using 4-fluorophenethylamine and acetyl chloride, 7-fluoro-1-methyl-1,2,3,4-tetrahydroisoquinoline was obtained. In accordance with the same procedures as in Preparation 20, the titled compound was obtained as pale yellow oil. (Yield: 69%) The product was used in the subsequent step without further purification. In accordance with the same procedures as in Steps 1, 2, and 3 of Preparation 21

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution of 1-methyl-7-fluoro-3,4-dihydroisoquinoline (2.4 g, 14.7 mmol) prepared in Step 2 in methanol (10 ml), sodium borohydride (0.28 g, 1 eq.) was portionwise added. The reaction mixture was stirred for 3 hours and 1N hydrochloric acid solution (20 ml) was added thereto. The reaction mixture was washed with dichloromethane. The water layer was adjusted to pH 12 with potassium hydroxide solution and extracted with dichloromethane. The extract was washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give 2.0 g of the titled compound. The reaction mixture was washed with dichloromethane extracted with dichloromethane The extract was washed with water dried over anhydrous sodium sulfate concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In close analogy to the procedure described in Example 1, 6-chloro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 7-fluoro-1-methyl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In close analogy to the procedure described in Example 1, 6-chloro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 7-fluoro-1-methyl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 80 mg (0.33 mmol) of 6-Bromo-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid, 66 mg (0.40 mmol) of 7-fluoro-1-methyl-1,2,3,4-tetrahydro-isoquinoline, 63 mg (0.33 mmol) of EDC and 50 mg (0.12 mmol) of HOBt in 2 mL of DMF is stirred at room temperature for 24 h. The mixture is concentrated in vacuo and the solid residue is partitioned between methylene chloride (3 mL) and saturated aqueous sodium hydrocarbonate solution (3 mL). The organic layer is separated, washed with 0.5 N HCl, water and brine and concentrated in vacuo. The mixture is concentrated in vacuo the solid residue is partitioned between methylene chloride (3 mL) and saturated aqueous sodium hydrocarbonate solution (3 mL) The organic layer is separated washed with 0.5 N HCl, water and brine concentrated in vacuo