Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[C:5]([F:12])[CH:4]=1)#[N:2].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)CC)C.Cl.[F:45][CH:46]([F:80])[CH:47]1[CH2:52][NH:51][CH2:50][CH2:49][N:48]1[CH2:53][CH:54]([N:58]1[CH:62]=[C:61]([C:63]2[C:64]3[CH:71]=[CH:70][N:69]([CH2:72][O:73][CH2:74][CH2:75][Si:76]([CH3:79])([CH3:78])[CH3:77])[C:65]=3[N:66]=[CH:67][N:68]=2)[CH:60]=[N:59]1)[CH2:55][C:56]#[N:57]>C1COCC1>[C:56]([CH2:55][CH:54]([N:58]1[CH:62]=[C:61]([C:63]2[C:64]3[CH:71]=[CH:70][N:69]([CH2:72][O:73][CH2:74][CH2:75][Si:76]([CH3:77])([CH3:79])[CH3:78])[C:65]=3[N:66]=[CH:67][N:68]=2)[CH:60]=[N:59]1)[CH2:53][N:48]1[CH2:49][CH2:50][N:51]([C:7]([C:6]2[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[F:12])=[O:9])[CH2:52][CH:47]1[CH:46]([F:45])[F:80])#[N:57]
Reactant: N#Cc1ccc(C(=O)O)c(F)c1
Reactant: C[Si](C)(C)CCOCn1ccc2c(-c3cnn(C(CC#N)CN4CCNCC4C(F)F)c3)ncnc21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C[Si](C)(C)CCOCn1ccc2c(-c3cnn(C(CC#N)CN4CCN(C(=O)c5ccc(C#N)cc5F)CC4C(F)F)c3)ncnc21
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A mixture of 4-cyano-2-fluorobenzoic acid (47.0 mg, 0.285 mmol, Alfa Aesar), N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (101 mg, 0.264 mmol) and triethylamine (0.170 mL, 1.22 mmol) in THF (2.5 mL) was stirred at RT for 15 min, and then 4-[2-(difluoromethyl)piperazin-1-yl]-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile hydrochloric acid salt (0.12 g, 0.20 mmol; a mixture of diastereomers from Step 7) was added. The mixture was stirred at RT for 1 h. The reaction was partitioned between ethyl acetate and water. The layers were separated, and the organic layer was washed with water, 0.1N NaOH, and brine; dried over sodium sulfate, decanted and concentrated. Flash chromatography on a 12 g silica gel cartridge, eluting with 0-80% solvent mixture [A] in hexanes ([A]=10% IPA: 50% EtOAc: 40% Hexanes); afforded desired product as a mixture of diastereomers (110 mg, 81%). The isomers were separated by chiral HPLC (Chiral Technologies Chiralcel OD-H, 20×250 mm, eluting with 30% EtOH/Hexanes at a flow rate of 10 mL/min and a loading of 20 mg/injection). Three peaks were obtained: Peak 1 retention time: 26.30 min, 19 mg; Peak 2 retention time: 33.82 min, 49 mg, mixture of 2 isomers; Peak 3 retention time 44.26 min, 29 mg. Peak 1: 1H NMR (300 MHz, CDCl3, rotamers): δ 8.84 (s, 0.4H), 8.83 (s, 0.6H), 8.32 (s, 1H), 8.31 (s, 0.4H), 8.30 (s, 0.6H), 7.79-7.32 (m, 4H), 6.79-6.76 (2d, 1H), 5.96 (td, 0.6H), 5.84 (br t, 0.4H), 5.67 (s, 2H), 4.68-4.55 (m, 1H), 4.51-4.21 (m, 1H), 3.61-0.75 (m, 14H), −0.07 (s, 9H); LCMS (M+H)+: 663.8. Peak 2 (mixture of two isomers and rotamers observed): 1H NMR (300 MHz, CDCl3): δ 8.84 (s, 0.814), 8.83 (s, 1.2H), 8.33 (s, 0.8H), 8.32 (s, 1.2H), 8.30 (s, 2H), 7.54-7.35 (m, 8H), 6.78 (d, 2H), 5.97 (td, 1.2H), 5.91 (td, 0.8H), 5.68 (s, 4H), 4.65-4.51 (m, 2H), 4.24-4.08 (m, 2H), 3.56 (dd, 4H), 3.47-0.80 (m, 24H), −0.07 (s, 18H); LCMS (M+H)+: 663.8. Peak 3: 1H NMR (300 MHz, CDCl3, rotamers): δ 8.84 (s, 0.4H), 8.83 (s, 0.6H), 8.32 (s, 1H), 8.31 (s, 0.4H), 8.30 (s, 0.6H), 7.79-7.32 (m, 4H), 6.79-6.76 (2d, 1H), 5.96 (td, 0.6H), 5.84 (br t, 0.4H), 5.67 (s, 2H), 4.68-4.55 (m, 1H), 4.51-4.21 (m, 1H), 3.61-0.75 (m, 14H), −0.07 (s, 9H); LCMS (M+H)+: 663.8.