Reaction SMILES: C(OCC1[C:18]2[C:13](=[CH:14][N:15]=[C:16]([C:19]([NH:21][OH:22])=[O:20])[CH:17]=2)[N:12]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[F:31])[CH:11]=1)C1C=CC=CC=1.S(Cl)(Cl)=O.Cl.Cl.[N:38]1C2C[C@@H](C(O)=O)NCC=2NC=1>CO>[F:31][C:25]1[CH:26]=[C:27]([F:30])[CH:28]=[CH:29][C:24]=1[CH2:23][N:12]1[C:13]2[CH:14]=[N:15][C:16]([C:19]([NH:21][OH:22])=[O:20])=[CH:17][C:18]=2[N:38]=[CH:11]1
Reactant: O=C(NO)c1cc2c(COCc3ccccc3)cn(Cc3ccc(F)cc3F)c2cn1
Reactant: O=C(O)[C@@H]1Cc2nc[nH]c2CN1
Agent: Cl
Solvent: O=S(Cl)Cl
Solvent: CO
Product: O=C(NO)c1cc2ncn(Cc3ccc(F)cc3F)c2cn1
Temperature: 25 °C
Yield: 100 %

Procedure:
(6S)-4,5,6,7-Tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid dihydrochloride. L-histidine (204.8 g, 1.32 mol) was added to water (1.2 L) and cooled on an ice/water bath. Concentrated hydrochloric acid (116.0 mL, 1.39 mol, 1.05 mol eqv.) was added slowly. Formaldehyde, 37 wt/wt % in water (112.5 g, 1.39 mol, 1.05 mol eqv.) was added in one portion. The reaction mixture was stirred for 30 min upon cooling on an ice/water bath, and then refluxed for 75 min. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was suspended in isopropanol (2 L) and HCl (400 mL of a 4 M solution in dioxane) for 30 min. The white solid was filtered and washed with ether. After drying in a vacuum oven (40° C.), the title product was obtained. (313.0 g, 99% yield, 95% pure). 1H NMR (DMSO-d6): δ: 3.05-3.33 (m, 2H), 4.30 (s, 2H), 4.54 (m, 1H), 9.00 (s, 1H), 12.60 (br s, 3H). LC-MS: Rt=0.59 min, and M+1=168.1 m/z (M+1 of free base). (b) Methyl (6S)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylate dihydrochloride. Thionylchloride (200 mL, 2.74 mol, 3.0 mol eqv.) was added dropwise to methanol (3.5 L), which was cooled to 0-5° C. (6S)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid dihydrochloride (210.0 g, 0.87 mol) was added, and the suspension was allowed to warm up to room temperature, and refluxed for 3.5 h. After cooling to room temperature, the solvent was removed under reduced pressure. The white residue was suspended in ether (3 L). The solid was filtered and washed with ether. After drying in a vacuum oven (40° C.), the title compound was obtained (225.0 g, 100% yield, 95% pure). 1H NMR (DMSO-d6): δ: 12.65 (br s, 2H), 9.04 (s, 1H), 4.71 (m, 1H), 4.33 (t, J=16.2 Hz, 2H), 3.81 (s, 3H), 3.10-3.33 (m, 2H), LC-MS: Rt=0.61 min, and M+1=182.1 m/z (M+1 of free base). (c) Methyl 3H-imidazo[4,5-c]pyridine-6-carboxylate. Methyl (6S)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylate dihydrochloride (156.5 g, 0.62 mol), triethylamine (445.0 g, 4.4 mol, 7.0 mol eqv.), selenium dioxide (158.2 g, 1.43 mol, 2.3 mol eqv.), and polyphosphatesilyl ether (PPSE) (15.0 g) were added to CCl4 (1.5 L). The mixture was refluxed for 6 h. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was suspended in methanol (1.5 L), and triethylamine was added to adjust to pH 8. The brown solid was filtered and washed well with methanol. This brown solid (117.0 g) was recrystallized from hot DMF (2 L)/140° C. The solution was filtered hot to remove black side product of selenium salt. Upon cooling to room temperature, the desired product crystallized out as a yellow solid (51.3 g, 47% yield, 95% pure). 1H NMR (DMSO-d6): δ: 13.20 (br s, 1H), 9.02 (s, 1H), 8.58 (s, 1H), 8.31 (s, 1H), 3.89 (s, 3H); LCMS: Rt=1.33 min, and M+1=178.1 m/ (d) Methyl 3-(2,4-difluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxylate and methyl 1-(2,4-difluorobenzyl)-1H-imidazo[4,5-c]pyridine-6-carboxylate. The title compounds were prepared by alkylation of methyll H-imidazo[4,5-c]pyridine-6-carboxylate with 2,4-difluorobenzyl bromide in a manner similar to step (a) of example 1. The two regioisomers were separated by column chromatograph using ethyl acetate as eluent and characterized by Roesy 1H NMR. Methyl 3-(2,4-difluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxylate: Rf: 0.29 (ethyl acetate); 1H NMR (CD3OD) δ: 9.02 (s, 1H), 8.70 (s, 1H), 8.34 (s, 1H), 7.53-7.59 (m, 1H), 7.30-7.33 (m, 1H), 7.09-7.12 (m, 1H), 5.71 (s, 2H), 3.87 (s, 3H). LCMS (API-ES, M+H+): 304.0. Methyl 1-(2,4-difluorobenzyl)-1H-imidazo[4,5-c]pyridine-6-carboxylate: Rf: 0.18 (ethyl acetate); 1H NMR (CD3OD) δ: 9.03 (s, 1H), 8.68 (s, 1H), 8.40 (s, 1H), 7.45-7.51 (m, 1H), 7.29-7.31 (m, 1H), 7.09-7.11 (m, 1H), 5.69 (s, 2H), 3.88 (s, 3H). LCMS (, API-ES, M+H+): 304.1. (e) 3-(2,4-Difluorobenzyl)-N-hydroxy-3H-imidazo[4,5-c]pyridine-6-carboxamide. The title compound was prepared from methyl 3-(2,4-difluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxylate in a manner similar to step (e) of example 11. 1H NMR (DMSO-d6) δ: 11.27 (s, 1H), 9.00 (s, 1H), 8.88 (s, 1H), 8.66 (s, 1H), 8.19 (s, 1H), 7.58 (m,1H), 7.31 (m, 1H), 7.11 (m, 1H), 5.70 (s, 2H). LCMS (API-ES, M+H+): 305.0. HRMS calcd for C14H11F2N4O2 (M+H) 305.0850, found 305.0837. HPLC: 100% purity.