2-piperidin-4-ylpropan-2-ol

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: 2-Chloro-4-morpholinopyrido[3,2-d]pyrimidine-6-carboxylic acid (0.12 g) was reacted with 2-(piperidin-4-yl)propan-2-ol (1.2 eq), HATU O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.2 eq) and DIPEA (3 eq) in DMF (3.2 mL) for 1 hour. The reaction was then extracted with EtOAc and bicarbonate solution and the organic layer was dried with Magnesium sulfate, filtered and concentrated to give (2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)(4-(2-hydroxypropan-2-yl)piperidin-1-yl)methanone in quantitative yield. The reaction was then extracted with EtOAc and bicarbonate solution the organic layer was dried with Magnesium sulfate filtered concentrated

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

Procedure: 2-Chloro-4-morpholinopyrido[3,2-d]pyrimidine-6-carboxylic acid (0.12 g) was reacted with 2-(piperidin-4-yl)propan-2-ol (1.2 eq), HATU O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.2 eq) and DIPEA (3 eq) in DMF (3.2 mL) for 1 hour. The reaction was then extracted with EtOAc and bicarbonate solution and the organic layer was dried with Magnesium sulfate, filtered and concentrated to give (2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)(4-(2-hydroxypropan-2-yl)piperidin-1-yl)methanone in quantitative yield. The reaction was then extracted with EtOAc and bicarbonate solution the organic layer was dried with Magnesium sulfate filtered concentrated

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

Procedure: Following General Procedure B, 4-(6-(bromomethyl)-2-chloropyrido[3,2-d]pyrimidin-4-yl)morpholine 7 and 2-(piperidin-4-yl)propan-2-ol were reacted to give 2-(1-((2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol. LCMS (MH+)=406.1. 1H-NMR (DMSO-d6): δ 8.02 (d, 1H), 7.83 (d, 1H), 4.46 (s, br, 4H), 4.01 (s, 1H), 3.78 (m, 4H), 3.68 (s, 2H), 2.88 (m, 2H), 1.96 (m, 2H), 1.65 (m, 2H), 1.25 (m, 3H), 1.03 (s, 6H) were reacted

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

Procedure: 2-((2-chloro-5-cyano-4-(3-oxopropyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (49 mg, 0.093 mmol) was taken up in TIIF (1 mL) and 2-(piperidin-4-yl)propan-2-ol (26.6 mg, 0.186 mmol), AcOH (5.32 μl, 0.093 mmol), and sodium cyanoborohydride (11.69 mg, 0.186 mmol) were added. The reaction was stirred at room temperature overnight. The reaction mixture was quenched with 2M K3PO4 solution and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-100% EtOAc/DCM then flushed with 10% MeOH/DCM; 24 g column). 2-((2-chloro-5-cyano-4-(3-(4-(2-hydroxypropan-2-yl)piperidin-1-yl)propyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (43 mg) was obtained as a yellow glass. were added The reaction mixture was quenched with 2M K3PO4 solution extracted with EtOAc The organic layer was dried over Na2SO4 filtered concentrated The material was purified by flash column chromatography (0-100% EtOAc/DCM then flushed with 10% MeOH/DCM