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To a mixture of 2-(5-benzyloxy-pyridin-2-yl)-N-hydroxy-acetamidine (50 mg, 0.19 mmol) described in Manufacturing Example 127-1-5 and a 5 N hydrochloric acid aqueous solution (1 mL) was added sodium nitrite (20 mg, 0.29 mmol) at 0° C., which was stirred for 20 minutes at 0° C. Sodium hydrogencarbonate and water were added to the reaction mixture at 0° C., which was extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure. To a tetrahydrofuran (3 mL) solution of this residue were added 3-ethynyl-pyridin-2,6-diamine (10 mg, 0.39 mmol) described in Manufacturing Example 13-1-3 and triethylamine (27 μL, 0.19 mmol), which was stirred for 40 minutes at 50° C. under nitrogen atmosphere. Water was added to the reaction mixture at room temperature, which was extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate: heptane=2:1), and then purified further by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid) to obtain the title compound (4.7 mg, 4.0%) as a ditrifluoroacetic acid salt.

1. extractionwhich was extracted with ethyl acetate
2. customThe organic layer was separated
3. washwashed with saturated aqueous sodium chloride
4. dry with materialdried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationThe filtrate was concentrated under a reduced pressure
7. stirringwas stirred for 40 minutes at 50° C. under nitrogen atmosphere
8. extractionwhich was extracted with ethyl acetate
9. customThe organic layer was separated
10. washwashed with saturated aqueous sodium chloride
11. dry with materialdried over anhydrous magnesium sulfate
12. filtrationfiltered
13. concentrationThe filtrate was concentrated under a reduced pressure
14. customThe residue was purified by NH silica gel column chromatography (ethyl acetate: heptane=2:1)
15. custompurified further by reverse-phase high performance liquid chromatography (
16. additioncontaining 0.1% trifluoroacetic acid)