[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([NH2:9])=[CH:4][N:3]=1.[CH3:10][C:11]([O:15]C1CCCCO1)([CH3:14])[CH:12]=O.C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>ClCCl.[Ti](Cl)(Cl)(Cl)Cl.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([NH:9][CH2:10][C:11]([CH3:14])([OH:15])[CH3:12])=[CH:4][N:3]=1To a mixture of 2,4-dichloropyrimidin-5-amine (542 mg, 3.31 mmol) and 2-methyl-2-(tetrahydro-2H-pyran-2-yloxy)propanal (740 mg, 4.30 mmol) in dichloromethane (10 ml) at 0° C. was added dropwise a solution of titanium tetrachloride (0.401 ml, 3.64 mmol) in dichloromethane (4 ml). After the reaction mixture was stirred at room temperature for 2 hours. Sodium cyanoborohydride (656 mg, 9.92 mmol) was added portionwise and the reaction mixture was stirred at room temperature for 16 hours. After the reaction mixture was diluted with dichloromethane, the reaction mixture was poured carefully into NaHCO3 aqueous solution. EtOAc was added and then the insoluble materials were filtered off. The phases of the filtrate were separated, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with water, dried and concentrated in vacuo to give a crude oil. The crude residue was purified by silica gel chromatography (hexane/ethyl acetate, 19:1 to 2:3) to afford 1-(2,4-dichloropyrimidin-5-ylamino)-2-methylpropan-2-ol (315 mg, 1.34 mmol, 40% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.15 (s, 6H) 3.16 (d, J=6.32 Hz, 2H) 4.64 (s, 1H) 5.60-5.68 (m, 1H) 8.31 (s, 1H).
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