N-piperidin-4-ylmethanesulfonamide;hydrochloride

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

Procedure: The title compound was prepared according to EXAMPLE 229 from 2-(S)-[(5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid (EXAMPLE 228) and N-piperidin-4-yl methanesulfonamide hydrochloride (Preparation 92). Purification gave the title compound as an off-white powder. m/z (ES+)=522.30 [M+H]+; RT=3.29 min. The title compound was prepared Purification

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

Procedure: The title compound was prepared according to EXAMPLE 229 from 2-(S)-[(5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid (EXAMPLE 228) and N-piperidin-4-yl methanesulfonamide hydrochloride (Preparation 92). Purification gave the title compound as an off-white powder. m/z (ES+)=522.30 [M+H]+; RT=3.29 min. The title compound was prepared Purification

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

Procedure: In a dried reaction flask, 2-chloro-4-(3-chloro-5-cyclopentyl-4,5-dihydro-1H-pyrazole-1-yl)benzonitrile (420 mg, 1 mmol), N-piperidine-4-ylmethanesulfonamide hydrochloride (280 mg, 1.30 mmol), DIEA (0.52 mL, 3 mmol), and HATU (418 mg, 1.1 mmol) were added to a mixed solvent of CH2Cl2 (10 mL) and DMF (5 mL). The mixture was stirred at room temperature for 3 hr. LC-MS monitored that the starting materials vanished. The solution was evaporated at reduced pressure. Water was added to the residue and the mixture was extracted with ethyl acetate. The combined organic phase was washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to produce a yellow powdery solid, which was washed with water and anhydrous ethyl ether to obtain a yellow powdery solid (532 mg) in 91.74% yield. The solution was evaporated at reduced pressure Water was added to the residue the mixture was extracted with ethyl acetate The combined organic phase was washed with water and brine dried over anhydrous sodium sulfate concentrated under reduced pressure to produce a yellow powdery solid, which was washed with water and anhydrous ethyl ether

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

Procedure: In a dried reaction flask, butyl 4-(methylsulfonamido)piperidine-1-carboxylate (2.53 g, 9.1 mmol) was dissolved in a mixed solvent of dichloromethane (20 mL) and methanol (5 mL). A dried HCl gas was passed thereto at room temperature for 2 hr, and a white solid was formed. The mixture was filtered and washed with dichloromethane and anhydrous ethyl ether, and dried to obtain a white powdery solid (1.88 g) in a 96.3% yield. a white solid was formed The mixture was filtered washed with dichloromethane and anhydrous ethyl ether dried

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

Procedure: The title compound was prepared according to EXAMPLE 229 from 2-(S)-[(5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid (EXAMPLE 228) and N-piperidin-4-yl methanesulfonamide hydrochloride (Preparation 92). Purification gave the title compound as an off-white powder. m/z (ES+)=522.30 [M+H]+; RT=3.29 min. The title compound was prepared Purification

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

Procedure: A stirred mixture of 7-acetyl-5-chloroquinolin-8-yl trifluoromethanesulfonate (0.16 g, 0.22 mmol, from Example 47, Step 2), N-piperidin-4-ylmethanesulfonamide hydrochloride (0.040 g, 0.19 mmol), palladium acetate (0.84 mg, 0.0037 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (3.5 mg, 0.0056 mmol), and cesium carbonate (0.23 g, 0.71 mmol) in tetrahydrofuran (4 mL) was heated at 65° C. overnight. The mixtures was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over MgSO4, evaporated and purified on silica gel (eluting with 0 to 5% methanol in dicholomethane) to give the desired product (27 mg, 38%). LCMS calculated for C17H21ClN3O3S (M+H)+: m/z=382.1; Found: 382.0. The mixtures was cooled filtered The filtrate was washed with brine dried over MgSO4 evaporated purified on silica gel (eluting with 0 to 5% methanol in dicholomethane)

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

Procedure: The title compound was prepared according to EXAMPLE 229 from 2-(S)-[(5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid (EXAMPLE 228) and N-piperidin-4-yl methanesulfonamide hydrochloride (Preparation 92). Purification gave the title compound as an off-white powder. m/z (ES+)=522.30 [M+H]+; RT=3.29 min. The title compound was prepared Purification