3-fluoroazetidine

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:; See reaction.notes.procedure_details.

Procedure: Following the procedure described for N-[2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-yl]-N′-methylpyrimidine-4,6-diamine, (6-chloropyrimidin-4-yl)-[2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-yl]amine and 3-fluoroazetidine with added DIPEA (103 μL, 0.6 mmol) were reacted to afford the title compound as a yellow solid (81 mg, 93% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.28 (br s, 1H), 9.14 (s, 1H), 8.29 (s, 1H), 7.94 (s, 1H), 7.80 (d, J=8.1 Hz, 2H), 7.70 (dd, J=9.1, 7.3 Hz, 2H), 7.16 (br s, 1H), 5.62-5.46 (m, 1H), 4.38 (ddd, J=21.3, 10.5, 5.9 Hz, 2H), 4.14 (d, J=10.5 Hz, 1H), 4.08 (d, J=10.5 Hz, 1H). LCMS (Method B): RT=3.16 min, m/z: 430 [M+H+]. were reacted

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

Procedure: A mixture of 2-(2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-6-yl)acetaldehyde (200 mg, 0.617 mmol) and 3-fluoroazetidine (95 mg, 1.23 mmol) in DCM (4 mL) was stirred at room temperature for 30 minutes under N2. Then Na(OAc)3BH (50 mg) was added to the mixture, and the mixture was stirred at room temperature for 1 hour. After dilution with water (30 mL) and extraction with EA (20 mL×3), the organic layer was washed with brine (30 mL*3), dried over Na2SO4 and concentrated. The residue was purified by column chromatography (PE:EA=1:1) to afford the desired product of 2-chloro-11-fluoro-6-(2-(3-fluoroazetidin-1-yl)ethyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (100 mg, yield: 43%). 1H-NMR (CDCl3, 400 MHz) δ 7.44 (d, J=8.0 Hz, 1H), 7.3 (s, 1H), 7.16 (d, J=8.0 Hz, 1H), 7.10 (t, J=4.8 Hz, J=2.7 Hz, 2H), 6.69˜6.74 (m, 1H), 5.11˜5.14 (m, 0.5H), 4.97˜4.50 (m, 0.5H), 4.87 (t, J=4.8 Hz, 1H), 3.57 (d, J=6.8 Hz, 1H), 3.33˜3.39 (m, 1H), 2.95˜3.06 (m, 2H), 2.2˜72.38 (m, 1H). MS (M+H)+: 374/376. the mixture was stirred at room temperature for 1 hour After dilution with water (30 mL) and extraction with EA (20 mL×3) the organic layer was washed with brine (30 mL*3) dried over Na2SO4 concentrated The residue was purified by column chromatography (PE:EA=1:1)

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

Procedure: Using 3-fluoro-azetidine and 5-(2-dimethylamino-[1,2,4]triazolo[1,5-a]pyridin-6-ylcarbamoyl)-1-methyl-1H-pyrazole-4-carboxylic acid, the title compound was prepared in the same manner as described for example 2. Light yellow solid (160 mg, 68%). MS: m/z=387 (M+H+).

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

Procedure: Using 3-fluoro-azetidine and 5-(2-dimethylamino-[1,2,4]triazolo[1,5-a]pyridin-6-ylcarbamoyl)-1-methyl-1H-pyrazole-4-carboxylic acid, the title compound was prepared in the same manner as described for example 2. Light yellow solid (160 mg, 68%). MS: m/z=387 (M+H+).

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

Procedure: Using 3-fluoro-azetidine and 1-methyl-5-(2-morpholin-4-yl-[1,2,4]triazolo[1,5-a]pyridin-6-ylcarbamoyl)-1H-pyrazole-4-carboxylic acid, the title compound was prepared in the same manner as described for example 2. Off-white solid (150 mg, 76%). MS: m/z=429 (M+H+).