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In a 25 mL round-bottomed flask, 2-(8-fluoro-2-{3-formyl-4-[1-methyl-5-(5-methyl-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydro-pyridazin-3-yl]-pyridin-2-yl}-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-methyl -propionitrile (800 mg, 1.35 mmol, 1.0 equiv.) was combined with dry DCM (25 ml) and dry methanol (5 mL) to give a light yellow solution. The reaction mixture was cooled to 0° C. and sodium borohydride (91.8 mg, 2.43 mmol, Eq: 1.8) was added. The reaction mixture was stirred at 0° C. for 40 min. and then was quenched with 2 mL saturated NH4Cl with stirring for 5 min. The reaction mixture was poured into 100 mL H2O and extracted with DCM (3×150 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude foam was taken up in 20 mL DCM and 15 mL methanol. To this mixture was added 200 mg of 10% Pd/C (Degussa brand). The reaction mixture was stirred at room temperature for 2 h. The solid was removed by filtration and washed several times with 10% methanol in DCM. The combined filtrate and washes were concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 0% to 4% MeOH holding gradient as each peak came off). Center cut fractions were concentrated to give a glass, which was triturated with ether to afford 2-(8-fluoro-2-{3-hydroxymethyl-4-[1-methyl-5-(5-methyl-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydro-pyridazin-3-yl]-pyridin-2-yl}-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-methyl-proprionitrile as an off-white solid. (M+H)+=596 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.81 (s, 6 H) 2.52 (s, 3 H) 2.94 (t, J=5.67 Hz, 2 H) 3.65 (d, J=2.27 Hz, 2 H) 3.90 (s, 3 H) 4.05-4.22 (m, 3 H) 4.42-4.60 (m, 2 H) 5.85 (s, 1 H) 6.66 (dd, J=7.55, 1.89 Hz, 1 H) 7.22 (dd, J=12.46, 1.89 Hz, 1 H) 7.35 (d, J=7.55 Hz, 1 H) 7.53 (d, J=1.89 Hz, 1 H) 7.62 (d, J=4.91 Hz, 1 H) 7.92 (s, 1 H) 7.99 (s, 1 H) 8.68 (d, J=4.91 Hz, 1 H).

1. customto give a light yellow solution
2. customwas quenched with 2 mL saturated NH4Cl
3. stirringwith stirring for 5 min
4. additionThe reaction mixture was poured into 100 mL H2O
5. extractionextracted with DCM (3×150 mL)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. concentrationconcentrated in vacuo
8. additionTo this mixture was added 200 mg of 10% Pd/C (Degussa brand)
9. stirringThe reaction mixture was stirred at room temperature for 2 h
10. customThe solid was removed by filtration
11. washwashed several times with 10% methanol in DCM
12. concentrationThe combined filtrate and washes were concentrated in vacuo
13. customThe crude material was purified by flash chromatography (silica gel, 40 g, 0% to 4% MeOH holding gradient as each peak
14. concentrationwere concentrated
15. customto give a glass, which
16. customwas triturated with ether