Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]([CH2:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[S:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1)(=[O:7])=[O:6].[C:21]([C:23]1[CH:24]=[CH:25][C:26](F)=[N:27][CH:28]=1)#[N:22].CCN(C(C)C)C(C)C.O>CS(C)=O>[C:21]([C:23]1[CH:24]=[CH:25][C:26]([NH:1][CH2:2][CH2:3][N:4]([CH2:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[S:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)(=[O:7])=[O:6])=[N:27][CH:28]=1)#[N:22]
Reactant: NCCN(CC1CCCCC1)S(=O)(=O)c1ccccn1
Reactant: N#Cc1ccc(F)nc1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: N#Cc1ccc(NCCN(CC2CCCCC2)S(=O)(=O)c2ccccn2)nc1
Temperature: 120 °C

Procedure:
The primary amine of N-(2-aminoethyl)-N-(cyclohexylmethyl)pyridine-2-sulfonamide (19) was arylated with 5-cyano-2-fluoropyridine on a 0.350 mmol scale. To a stirring solution of the primary amine (1 equiv) in DMSO (0.2 M) were added the aryl fluoride (1.2 equiv) and DIPEA (3 equiv). The reaction mixture was heated to 120° C. for 48 h. After allowing the reaction to cool, H2O was added, and the crude product was extracted with EtOAc (×3). The EtOAc extractions were combined, washed with water (×3), brine, dried (Na2SO4), filtered and concentrated. After work-up and purification by silica gel flash column chromatography (eluent CH2Cl2/MeOH/NH4OH, 192:7:1), N-(2-(5-cyanopyridin-2-ylamino)ethyl)-N-(cyclohexylmethyl)pyridine-2-sulfonamide was obtained as a colorless gum (115 mg, 82%): δH (500 MHz, DMSO-d6) 0.78-0.82 (m, 2H, 2 CH (cyclohexylmethyl)), 1.09 (br, 3H, 3 CH (cyclohexylmethyl)), 1.57-1.63 (m, 6H, 6 CH (cyclohexylmethyl)), 3.06 (d, J=7.5 Hz, 2H, NCH2CH (cyclohexylmethyl)), 3.37-3.47 (m, 4H, SO2NCH2CH2N), 6.50 (t, J=8.5 Hz, NH), 6.87 (d, J=9.0 Hz, 1H, CH (Ar)), 7.61-7.66 (m, 3H, 2 CH (Ar), CH (Py)), 7.92 (d, J=7.5 Hz, 1H, CH (Py)), 8.06 (m, 1H, CH (Py)), 8.36 (m, 1H, CH (Ar)), 8.71 (m, 1H, CH (Py)); δC (125 MHz, DMSO-d6) 25.1, 25.8, 30.0, 35.6, 47.7, 54.7, 55.5, 69.3, 94.7, 108.7, 118.7, 122.1, 126.9, 138.5, 150.0, 152.8, 157.0, 159.6; HRMS (ES+) calcd for [C20H25N5O2S+H] 400.1807. found 400.1795. N-(2-(5-Cyanopyridin-2-ylamino)ethyl)-N-(cyclohexylmethyl)pyridine-2-sulfonamide was then alkylated with 5-chloromethyl-1H-imidazole.HCl on a 0.240 mmol scale. The secondary aniline (1 equiv) was dissolved in DMF (0.07 M), then the reaction was cooled to 0° C. After 15 min, NaH (3 eq.) was added in one portion. After a further 15 min, 5-chloromethyl-1-methyl-1H-imidazole.HCl (1.1 eq) was added. The reaction was allowed to stir at 0° C. from 2-3 h, when TLC indicated the reaction was complete or had stalled. Upon quenching the reaction with brine (approximately 1 mL), the reaction was diluted with water and extracted with EtOAc (×3). The EtOAc extractions were combined, and washed with 5% NaHCO3 (×3), brine, dried (Na2SO4), filtered and concentrated. After work-up and chromatography over silica gel (eluent CH2Cl2/MeOH/NH4OH, 192:7:1), the title compound N-(2-((5-cyanopyridin-2-yl)((1-methyl-1H-imidazol-5-yl)methyl)amino)ethyl)-N-(cyclohexylmethyl)pyridine-2-sulfonamide was afforded as a white foam (110 mg, 93%): δH (500 MHz, CDCl3) 0.75-0.83 (m, 2H, 2 CH (cyclohexylmethyl)), 1.07-1.16 (m, 3H, 3 CH (cyclohexylmethyl)), 1.33-1.43 (m, 1H, CH (cyclohexylmethyl)), 1.59-1.65 (m, 5H, 5 CH (cyclohexylmethyl)), 2.94 (d, J=7.0 Hz, 2H, NCH2CH (cyclohexylmethyl)), 3.28 (t, J=8.1 Hz, 2H, SO2NCH2CH2N), 3.55 (s, 3H, CH3 (Im)), 3.70 (t, J=8.1 Hz, 2H, SO2NCH2CH2N), 4.89 (s, 2H, CH2Im), 6.81 (d, J=9.0 Hz, 1H, CH (Ar)), 6.97 (s, 1H, CH (Im)), 7.45 (m, 1H, CH (Im)), 7.57 (s, 1H, CH (Ar)), 7.64 (m, 1H, CH (Ar)), 7.89-7.85 (m, 2H, 2 CH (Py)), 8.39-8.38 (m, 1H, CH (Ar)), 8.60 (m, 1H, CH (Py)); δC (125 MHz, CDCl3) 25.6, 26.2, 30.5, 32.0, 36.6, 40.9, 47.2, 56.8, 97.1, 105.9, 118.2, 122.5, 126.6, 127.4, 128.8, 137.9, 138.9, 140.2, 149.9, 152.3, 157.5, 158.4, 162.4; HRMS (ES+) calcd for [C25H31N7O2S+H] 494.2338. found 494.2313; HPLC (I) tR=18.15 min (99.5%), (II) tR=34.66 min (97.4%)