4-fluoropiperidine

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

Procedure: The title compound was prepared from 3-[7-oxo-4-(3-trifluoromethyl-phenyl)-[1,4]diazepan-1-yl]-propionaldehyde (Example 34C) and 4-fluoropiperidine in analogy to example 34D. MS: 402.2 (MH+).

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Fluoropiperidine (0.7 g., 0.005 mole) was dissolved in a mixture of 3 ml. of dioxane and 2 ml. of water containing cyanoacetic acid (0.43 g., 0.005 mole). The solution was heated to 65° C. and carbon dioxide evolution began. It was maintained at 60°-65° C. for 21/2 hours and allowed to stand overnight. A solid gummy residue, 1 gm., was obtained upon stripping in a bath at 55° C. and at 1 mm. It was taken up in a small amount of water, made alkaline with sodium bicarbonate and extracted with ether. The organic layer was water washed and dried over anhydrous sodium sulfate. After solvent stripping, the product was obtained as a colorless oil, 0.7 g., of analytical purity. It was maintained at 60°-65° C. for 21/2 hours , was obtained upon stripping in a bath at 55° C. and at 1 mm extracted with ether washed dried over anhydrous sodium sulfate After solvent stripping, the product was obtained as a colorless oil, 0.7 g

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

Procedure: The title compound was prepared by a procedure similar to that described for E13 starting from 2-(8-((3,4-difluorobenzyl)oxy)-6-oxo-2,3,4,6-tetrahydro-1H-pyrimido[1,6-a]pyrimidin-1-yl)acetic acid and 4-fluoropiperidine.

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

Procedure: To a microwave reaction vessel was added ethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (3.7 g, 13 mmol), 6-bromoquinolin-2-amine (2.0 g, 9.0 mmol), PdCl2(PPh(t-Bu)2)2 (0.084 g, 0.13 mmol), potassium acetate (1.8 g, 18 mmol), EtOH (9.9 ml, 170 mmol) and water (2.4 ml, 134 mmol). The reaction mixture was heated at 85° C. for 8 h, and was then partitioned between EtOAc and water. The organic layer was washed with water and brine and allowed to stand for 72 h. The supernatant was decanted from the resulting precipitate and the precipitate was dried in vacuo to give ethyl 2-(2-aminoquinolin-6-yl)benzoate. Step 2 6-(2-Ethoxyphenyl)quinolin-2-amine (1.0 g, 3.8 mmol) was taken up in THF and then 5N NaOH was added and the solution was stirred for 72 h. DCM was added and the solid was filtered to give ethyl 2-(2-aminoquinolin-6-yl)benzoate. Step 3 A solution of 2-(2-aminoquinolin-6-yl)benzoic acid (50 mg, 0.19 mmol), 4-fluoropiperidine (25 mg, 0.24 mmol), HATU (91 mg, 0.24 mmol), DIEA (100 uL, 0.57 mmol), and DMF (1 mL) was heated in a shaker oven at 60° C. for 1 h. The resulting solution was purified by HPLC (CH3CN/water modified with 0.1% TFA) to give (2-(2-aminoquinolin-6-yl)phenyl)(4-fluoropiperidin-1-yl)methanone. MS (ESI, pos. ion) m/z: 350 (M+1). The resulting solution was purified by HPLC (CH3CN/water modified with 0.1% TFA)