(2-piperidin-1-ylphenyl)methanamine

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

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

Procedure: A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (150 mg, 0.58 mmol), 2-piperidin-1-yl-benzylamine (122 mg, 0.64 mmol), Pd2(dba)3 (53 mg, 0.058 mmol), rac-BINAP (108 mg, 0.17 mmol) and NaOt-Bu (251 mg, 2.61 mmol) in DMA (6 mL) was heated at 80° C. for 1 h. The mixture was allowed to cool, diluted with EtOAc (25 mL) and washed with water (25 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated. Chromatography on silica (EtOAc/hexanes) yielded the title compound. 4-Chloro-6-(2-piperidin-1-yl-benzylamino)-2H-phthalazin-1-one: 62 mg (29.0%): m/z (M+H)=369. 1H-NMR (DMSO-d6) δ: 12.35 (s, 1H), 7.90 (d, 1H), 7.77 (m, 1H), 7.32 (dd, 1H), 7.15 (m, 3H), 6.96 (m, 1H) 6.62 (s, 1H), 4.41 (d, 2H), 1.71 (m, 4H), 1.55 (m, 2H). to cool washed with water (25 mL) The organic layer was dried over anhydrous sodium sulfate concentrated

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

Procedure: A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (150 mg, 0.58 mmol), 2-piperidin-1-yl-benzylamine (122 mg, 0.64 mmol), Pd2(dba)3 (53 mg, 0.058 mmol), rac-BINAP (108 mg, 0.17 mmol) and NaOt-Bu (251 mg, 2.61 mmol) in DMA (6 mL) was heated at 80° C. for 1 h. The mixture was allowed to cool, diluted with EtOAc (25 mL) and washed with water (25 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated. Chromatography on silica (EtOAc/hexanes) yielded the title compound. 4-Chloro-6-(2-piperidin-1-yl-benzylamino)-2H-phthalazin-1-one: 62 mg (29.0%): m/z (M+H)=369. 1H-NMR (DMSO-d6) δ: 12.35 (s, 1H), 7.90 (d, 1H), 7.77 (m, 1H), 7.32 (dd, 1H), 7.15 (m, 3H), 6.96 (m, 1H) 6.62 (s, 1H), 4.41 (d, 2H), 1.71 (m, 4H), 1.55 (m, 2H). to cool washed with water (25 mL) The organic layer was dried over anhydrous sodium sulfate concentrated

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-2-benzyl 3-ethyl 8-(2-amino-6-chloropyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (200 mg, 0.6 mmol) and [2-(1-piperidinyl)phenyl]methanamine (CAS#: 72752-54-6) (105 mg, 0.8 mmol) in i-PrOH (2 mL) was added diisopropylethyl amine (0.5 mL). The reaction was heated to 120° C. for 2 h followed by heating to 140° C. for 1 h under microwave conditions, then cooled to RT and concentrated in vacuo. Purification by normal phase silica gel column (EtOAc/heptane) provided (S)-2-benzyl 3-ethyl 8-(2-amino-6-((2-(piperidin-1-yl)benzyl)amino)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as a white solid. by heating to 140° C. for 1 h under microwave conditions cooled to RT concentrated in vacuo Purification by normal phase silica gel column (EtOAc/heptane)