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A solution of trimethylaluminium (2M in hexane) (0.322 mL, 0.64 mmol) was added dropwise to a stirred solution of 5-chloropyridin-2-amine (CAS no. 1072-98-6) (79 mg, 0.62 mmol) in toluene (5 mL) at 0° C., over a period of 1 minute under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. A solution of (2S)-methyl 3-ethoxy-2-(1-(3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate (Intermediate Q1) (230 mg, 0.56 mmol) in toluene (5 mL) was added dropwise over a period of 2 minutes. The resulting solution was stirred at 0° C. for 10 minutes, allowed to warm to ambient temperature and then heated at 60° C. for 20 hours. The resulting mixture was allowed to cool and 1M citric acid (10 mL) added with vigorous stirring. Ethyl acetate (35 mL) and water (10 mL) were added and the organic phase was separated, washed with water (20 mL) and brine (20 mL), dried (MgSO4) and evaporated. The residue was purified by flash silica chromatography, eluting with 50 to 100% ethyl acetate in isohexane and then chiral preparative HPLC to give the product (90 mg, 31%). 1H NMR (400 MHz, CDCl3) δ 1.22 (3H, t), 3.60-3.68 (2H, m), 4.06-4.15 (2H, m), 6.05 (1H, t), 7.64-7.70 (2H, m), 8.22-8.25 (2H, m), 8.29 (1H, dd), 8.43 (1H, s), 8.62 (1H, s), 8.84 (1H, s)8.89 (1H, dd); m/z (ESI+) (M+H)+=508: HPLC tR=2.35 min.

1. stirringThe resulting solution was stirred at 0° C. for 10 minutes
2. temperatureto warm to ambient temperature
3. temperatureheated at 60° C. for 20 hours
4. temperatureto cool
5. customthe organic phase was separated
6. washwashed with water (20 mL) and brine (20 mL)
7. dry with materialdried (MgSO4)
8. customevaporated
9. customThe residue was purified by flash silica chromatography
10. washeluting with 50 to 100% ethyl acetate in isohexane