(2S)-2-hydroxypropanamide

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

Procedure: A mixture of (2S)-2-hydroxypropanamide (86.6 mg, 0.972 mmol) and triethyloxonium tetrafluoroborate (185 mg, 0.972 mmol) in THF (2 mL) was stirred at room temperature for 2 h. The solvent was removed and the residue dissolved in ethanol (0.50 mL) and added to a suspension of {(2R,5S)-5-[(6-aminothieno[3,2-b]pyridin-7-yl)amino]tetrahydro-2H-pyran-2-yl}methanol (65.0 mg, 0.233 mmol) in ethanol (1.8 mL). The mixture was stirred at 80° C. for 1 h. The mixture was cooled to room temperature, diluted with methanol, and purified with prep-LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product as white solid (45 mg, 58%). LCMS calculated for C16H20N3O3S (M+H)+: m/z=334.1. Found: 334. The solvent was removed the residue dissolved in ethanol (0.50 mL) The mixture was stirred at 80° C. for 1 h The mixture was cooled to room temperature purified with prep-LCMS (XBridge C18 column eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

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

Procedure: A mixture of (2S)-2-hydroxypropanamide (86.6 mg, 0.972 mmol) and triethyloxonium tetrafluoroborate (185 mg, 0.972 mmol) in THF (2 mL) was stirred at room temperature for 2 h. The solvent was removed and the residue dissolved in ethanol (0.50 mL) and added to a suspension of {(2R,5S)-5-[(6-aminothieno[3,2-b]pyridin-7-yl)amino]tetrahydro-2H-pyran-2-yl}methanol (65.0 mg, 0.233 mmol) in ethanol (1.8 mL). The mixture was stirred at 80° C. for 1 h. The mixture was cooled to room temperature, diluted with methanol, and purified with prep-LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product as white solid (45 mg, 58%). LCMS calculated for C16H20N3O3S (M+H)+: m/z=334.1. Found: 334. The solvent was removed the residue dissolved in ethanol (0.50 mL) The mixture was stirred at 80° C. for 1 h The mixture was cooled to room temperature purified with prep-LCMS (XBridge C18 column eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

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

Procedure: prepared by reaction of 2,6-dimethoxybenzaldehyde with (S)-(−)-2-hydroxypropionamide; LC-MS: tR=0.45 min; [M+H]+=238.28.

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

Procedure: A solution of (S)-2-hydroxypropanamide (13-1) (30 g, 337 mmol) and tert-butyldimethylchlorosilane (66.0 g, 438 mmol) in pyridine (101 ml, 1246 mmol) and DMF (90 ml) was stirred at room temperature for 16 h. The reaction mixture was filtered to remove insolubles and the filtrate was partitioned between saturated aqueous sodium bicarbonate solution (500 mL) and EtOAc (500 mL). The organic layer was washed with saturated aqueous sodium bicarbonate solution (2×100 mL), brine (3×100 mL) and water (3×100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to afford 13-2 as a viscous yellow oil. MS: m/z=204.0 (M+H). The reaction mixture was filtered to remove insolubles the filtrate was partitioned between saturated aqueous sodium bicarbonate solution (500 mL) and EtOAc (500 mL) The organic layer was washed with saturated aqueous sodium bicarbonate solution (2×100 mL), brine (3×100 mL) and water (3×100 mL) The organic layer was dried over sodium sulfate filtered concentrated

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

Procedure: A mixture of (2S)-2-hydroxypropanamide (86.6 mg, 0.972 mmol) and triethyloxonium tetrafluoroborate (185 mg, 0.972 mmol) in THF (2 mL) was stirred at room temperature for 2 h. The solvent was removed and the residue dissolved in ethanol (0.50 mL) and added to a suspension of {(2R,5S)-5-[(6-aminothieno[3,2-b]pyridin-7-yl)amino]tetrahydro-2H-pyran-2-yl}methanol (65.0 mg, 0.233 mmol) in ethanol (1.8 mL). The mixture was stirred at 80° C. for 1 h. The mixture was cooled to room temperature, diluted with methanol, and purified with prep-LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product as white solid (45 mg, 58%). LCMS calculated for C16H20N3O3S (M+H)+: m/z=334.1. Found: 334. The solvent was removed the residue dissolved in ethanol (0.50 mL) The mixture was stirred at 80° C. for 1 h The mixture was cooled to room temperature purified with prep-LCMS (XBridge C18 column eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)