Reaction SMILES: Cl.Cl.[N:3]1[C:8]2[NH:9][CH:10]=[CH:11][C:7]=2[C:6]([C:12]2[CH:13]=[N:14][N:15]([C:17]3([CH2:21][C:22]#[N:23])[CH2:20][NH:19][CH2:18]3)[CH:16]=2)=[N:5][CH:4]=1.C(N(CC)CC)C.[F:31][C:32]1[C:46]([C:47]([F:50])([F:49])[F:48])=[N:45][CH:44]=[CH:43][C:33]=1[C:34]([N:36]1[CH2:41][CH2:40][C:39](=O)[CH2:38][CH2:37]1)=[O:35].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[N:3]1[C:8]2[NH:9][CH:10]=[CH:11][C:7]=2[C:6]([C:12]2[CH:13]=[N:14][N:15]([C:17]3([CH2:21][C:22]#[N:23])[CH2:20][N:19]([CH:39]4[CH2:40][CH2:41][N:36]([C:34](=[O:35])[C:33]5[CH:43]=[CH:44][N:45]=[C:46]([C:47]([F:50])([F:49])[F:48])[C:32]=5[F:31])[CH2:37][CH2:38]4)[CH2:18]3)[CH:16]=2)=[N:5][CH:4]=1
Reactant: O=C1CCN(C(=O)c2ccnc(C(F)(F)F)c2F)CC1
Reactant: N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CNC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a 0.5-L flask equipped with a nitrogen inlet, a thermocouple, an additional funnel, and a mechanical stirrer were added 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile dihydrochloride salt (6, 20 g, 56.78 mmol), dichloromethane (200 mL) and triethylamine (TEA, 16.62 mL, 119.2 mmol, 2.1 equiv) at ambient temperature. The mixture was stirred at ambient temperature for 30 minutes before 1-(3-fluoro-2-(trifluoromethyl)-isonicotinoyl)piperidin-4-one (7, 17.15 g, 57.91 mmol, 1.02 equiv) was added to the mixture. The mixture was then treated with sodium triacetoxyborohydride (25.34 g, 113.6 mmol, 2.0 equiv) in 5 minutes at ambient temperature (below 26° C.). The resulting reaction mixture was stirred at ambient temperature for 2 hours. After the reaction was complete as monitored by HPLC, the reaction mixture was quenched with saturated NaHCO3 aqueous solution (200 mL). The two phases were separated and the aqueous phase was extracted with methylene chloride (200 mL). The combined organic phase was washed with 4% brine (100 mL) followed by solvent switch of methylene chloride to acetone by distillation. The resulting solution of the desired crude product (8) in acetone was directly used for the subsequent adipate salt formation. A small portion of solution was purified by column chromatography (SiO2, 0-10% of MeOH in EtOAc gradient elution) to afford the analytically pure 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(1-(3-fluoro-2-(trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin-3-yl)acetonitrile (8 free base) as an off-white solid. For 8: 1H NMR (400 MHz, DMSO-d6) δ 12.17 (d, J=2.8 Hz, 1H), 8.85 (s, 1H), 8.70 (m, 2H), 8.45 (s, 1H), 7.93 (t, J=4.7 Hz, 1H), 7.63 (dd, J=3.6, 2.3 Hz, 1H), 7.09 (dd, J=3.6, 1.7 Hz, 1H), 4.10 (m, 1H), 3.78 (d, J=7.9 Hz, 2H), 3.61 (t, J=7.9 Hz, 1H), 3.58 (s, 2H), 3.46 (m, 1H), 3.28 (t, J=10.5 Hz, 1H), 3.09 (ddd, J=13.2, 9.5, 3.1 Hz, 1H), 2.58 (m, 1H), 1.83-1.75 (m, 1H), 1.70-1.63 (m, 1H), 1.35-1.21 (m, 2H) ppm; 13C NMR (101 MHz, DMSO-d6) δ 160.28, (153.51, 150.86), 152.20, 150.94, 149.62, (146.30, 146.25), 139.48, (134.78, 134.61), (135.04, 134.92, 134.72, 134.60, 134.38, 134.26, 134.03, 133.92), 129.22, 127.62, 126.84, 121.99, 122.04, (124.77, 122.02, 119.19, 116.52), 117.39, 113.00, 99.99, 61.47, 60.49, 57.05, 44.23, 28.62, 27.88, 27.19 ppm; C26H23F4N9O (MW, 553.51), LCMS (EI) m/e 554.1 (M++H).