[ClH:1].Cl.[NH:3]1[C:7]2=[CH:8][N:9]=[CH:10][CH:11]=[C:6]2[CH:5]=[C:4]1[CH:12]([NH2:14])[CH3:13].[C:15](O)(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=1.C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.CN(C1C=CC=CN=1)C.Cl>C(Cl)Cl.CCOC(C)=O.CCO.CCOCC>[ClH:1].[ClH:1].[NH:3]1[C:7]2=[CH:8][N:9]=[CH:10][CH:11]=[C:6]2[CH:5]=[C:4]1[CH:12]([NH:14][C:15](=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=1)[CH3:13]A mixture of 1-(1H-pyrrolo[2,3-c]pyridin-2-yl)ethylamine dihydrochloride (Example 75) (74 mg, 0.32 mmol), nicotinic acid (41 mg, 0.33 mmol), diisopropylethylamine (0.28 mL, 0.38 mmol), EDCI (73 mg, 0.38 mmol) and dimethylaminopyridine (catalytic amount) in methylene chloride (2.8 mL) was stirred under a nitrogen atmosphere overnight (18 h). The reaction mixture was diluted with EtOAc and extracted with 1 N HCl. The acidic extracts were washed with EtOAc, and then made basic with 15% NaOH. The aqueous layer was extracted with CH2Cl2 (3×). The combined extracts were dried over Na2SO4. Filtration and concentration gave a crude yellow oil. Initial purification by Biotage chromatography (KP-NH silica) provided an impure product. The mixture was dissolved in EtOH and 2.0 M HCl in Et2O (0.34 mL) was added. The mixture was concentrated and then crystallized from acetone/methanol (9:1) to provide N-[1-(1H-pyrrolo[2,3-c]pyridin-2-yl)ethyl]nicotinamide dihydrochloride (12 mg, 11%) as a light yellow solid: 1H NMR (300 MHz, CD3OD) δ3.64 (3H, d, J=7.1 Hz), 5.65 (1H, q, J=7.0 Hz), 6.98 (1H, s), 8.03-8.20 (3H, m), 8.94-9.02 (3H, m), 9.34 (1H, s); ESI MS m/z 267 [C15H14N4O+H]+; HPLC (Method A) >99% (AUC), tR=9.19 min.
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