Hydrochloric Acid → HCID 178470385, compound

HRID 2377977Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([C:12]2[C:13]([O:19]C)=[N:14][CH:15]=[CH:16][C:17]=2I)=[N:9][C:10]=1[CH3:11])=[O:5])[CH3:2].Cl.C(N(CC)CC)C.[NH2:29][CH2:30][C@H:31]([C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[CH:34]=1)[OH:32]>C(O)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([C:12]2[C:13](=[O:19])[NH:14][CH:15]=[CH:16][C:17]=2[NH:29][CH2:30][CH:31]([C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[CH:34]=2)[OH:32])=[N:9][C:10]=1[CH3:11])=[O:5])[CH3:2]

Participants

Conditions

Temperature: 65 °C

Procedure

2-(4-Iodo-2-methoxy-pyridin-3-yl)-5-methyl-3H-imidazole-4-carboxylic acid ethyl ester (0.020 g, 0.052 mmol) was dissolved in acetic acid (1 mL) and concentrated hydrochloric acid (1 mL) and this mixture was stirred at reflux for 2 hours. The mixture was then evaporated and the residue was dissolved in N,N-dimethylformamide (2 mL) and treated with triethylamine (˜22 μL, 0.155 mmol) and the hydrochloric acid salt of (S)-2-amino-1-[3-chlorophenyl]ethanol (0.020 g, 0.096 mmol). The mixture was heated at 65° C. overnight, then the solvent was evaporated and the residue was purified by Prep HPLC (ammonium acetate/acetonitrile/water) to give the title compound (0.003 g, 14%) as a white solid. HPLC 100% (220 nm), LCMS (+ESI, M+H+) m/z 417; 1H NMR (400 MHz, methanol-d4) δ (ppm) (mixture of tautomers): 1.40 and 1.43 (3H, 2t, J=7.1 Hz), 2.49 and 2.61 (3H, 2s), 3.61-3.72 (2H, m), 4.35 and 4.39 (2H, q, J=7.1 Hz), 4.95-4.97 (1H, m), 6.21 and 6.23 (1H, 2d, J=7.6 Hz), 7.19-7.55 (5H, m).

Workup

temperatureat reflux for 2 hours
customThe mixture was then evaporated
dissolutionthe residue was dissolved in N,N-dimethylformamide (2 mL)
customthe solvent was evaporated
customthe residue was purified by Prep HPLC (ammonium acetate/acetonitrile/water)

Sources & evidence

ORD record: ord-c3bf78cb948a4cd9a80c70abdc198cc7
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07470713B2

Reaction notes

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