Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:43]([CH3:47])([CH3:46])[C:44]#[N:45])[CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:24]=[C:23]([NH:25][C:26]4[CH:38]=[C:29]5[CH2:30][N:31]([CH:34]6[CH2:37][O:36][CH2:35]6)[CH2:32][CH2:33][N:28]5[N:27]=4)[C:22](=[O:39])[N:21]([CH3:40])[N:20]=3)[C:14]=1[CH:41]=[O:42])[CH:8]=[CH:7]2.CO.[BH4-].[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([C:43]([CH3:47])([CH3:46])[C:44]#[N:45])[CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:24]=[C:23]([NH:25][C:26]4[CH:38]=[C:29]5[CH2:30][N:31]([CH:34]6[CH2:35][O:36][CH2:37]6)[CH2:32][CH2:33][N:28]5[N:27]=4)[C:22](=[O:39])[N:21]([CH3:40])[N:20]=3)[C:14]=1[CH2:41][OH:42])[CH:8]=[CH:7]2
Reactant: Cn1nc(-c2cccc(-n3ccc4cc(C(C)(C)C#N)cc(F)c4c3=O)c2C=O)cc(Nc2cc3n(n2)CCN(C2COC2)C3)c1=O
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: Cn1nc(-c2cccc(-n3ccc4cc(C(C)(C)C#N)cc(F)c4c3=O)c2CO)cc(Nc2cc3n(n2)CCN(C2COC2)C3)c1=O
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 19.9 %

Procedure:
6-chloro-2-methyl-4-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-pyridazin-3(2H)-one (prepared as described in example 60, 65 mg, 194 μmol) bis(pinacolato)diboron (54.1 mg, 213 μmol) and potassium acetate (57.0 mg, 581 μmol) were suspended in dioxane (9 ml). The reaction mixture was degassed under argon. X-PHOS (13.8 mg, 29.0 μmol) and palladium(II) acetate (2.17 mg, 9.68 μmol) were added and the reaction mixture was stirred at 100° C. (external temperature) for 45 min under an argon atmosphere. LCMS (taken in methanol) showed some conversion to boronic acid (M+1=347) and some of the undesired 2-methyl-4-(5-oxetan-3-yl-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazin-2-ylamino)-2H-pyridazin-3-one. Heating was turned down to 80° C. The flask was raised out of the heating bath, but continued stirring. 2-(2-(3-bromo-2-formylphenyl)-8-fluoro-1-oxo-1,2-dihydroisoquinolin-6-yl)-2-methylpropanenitrile (prepared as describe in example 15, 80 mg, 194 μmol) in 2 mL dioxanes and potassium carbonate (80.3 mg, 581 μmol) were added, followed by 1 mL H2O. Tricyclohexylphosphine (5.43 mg, 19.4 μmol) and bis(dibenzylideneacetone)-palladium (0) (5.57 mg, 9.68 μmol) were added. The reaction mixture was heated with vigorous stirring at 80° C. for 1.5 h. The crude reaction was poured onto H2O and EtOAc and extracted 3 times with EtOAc and 1 time with DCM. The combined organic extracts were washed with brine and dried over MgSO4. The crude material was purified by flash chromatography (silica gel, 24 g, 1% to 5% MeOH in DCM) to afford approx. 90 mg the intermediate 2-(8-fluoro-2-(2-formyl-3-(1-methyl-5-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)phenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-2-methylpropanenitrile. In a 25 mL round-bottomed flask, 2-(8-fluoro-2-(2-formyl-3-(1-methyl-5-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)phenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-2-methylpropanenitrile (90 mg, 142 μmol) was combined with dry CH2Cl2 (2 ml) and dry MeOH (0.5 mL) to give a light yellow solution. The solution was cooled to 0° C. Sodium borohydride (9.66 mg, 255 μmol) was added. The reaction mixture was stirred at 0° C. for 40 min. Complete by LCMS. Quenched with sat'd NH4Cl. The reaction mixture was poured into 25 mL H2O and extracted with DCM (2×50 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 0% to 3% MeOH). Pure fractions were concentrated to give a glass, which was dissolved in 1 mL DCM and precipitated with 20 mL ether to afford the desired product (18 mg) as a white solid. (M+H)+=637 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.81 (s, 6H) 2.90 (t, J=5.48 Hz, 2H) 3.55-3.71 (m, 2H) 3.77-3.86 (m, 1H) 3.89 (s, 3H) 4.17 (t, J=5.48 Hz, 2H) 4.26-4.42 (m, 2H) 4.66-4.87 (m, 4H) 5.83 (s, 1H) 6.62 (dd, J=7.55, 1.89 Hz, 1H) 7.22 (dd, J=12.28, 1.70 Hz, 1H) 7.34 (d, J=7.18 Hz, 1H) 7.41 (dd, J=7.74, 1.32 Hz, 1H) 7.50-7.61 (m, 2H) 7.63-7.72 (m, 1H) 7.85 (s, 1H) 7.95 (s, 1H).