Hydrochloric Acid → 4-chloro-3-[6-(7-ethyl-2,7-diaza-spiro[4.4]non-2-yl)-4-methyl-1H-benzoimidazol-2-yl]-1H-pyridin-2-one

HRID 470307Notes

Reaction equation

Cl[C:2]1[C:7]([C:8]2[NH:12][C:11]3[CH:13]=[C:14]([N:18]4[CH2:22][CH2:21][C:20]5([CH2:26][CH2:25][N:24]([CH2:27][CH3:28])[CH2:23]5)[CH2:19]4)[CH:15]=[C:16]([CH3:17])[C:10]=3[N:9]=2)=[C:6](I)[CH:5]=[CH:4][N:3]=1.[ClH:30].[O:31]1CCOCC1>O>[Cl:30][C:6]1[CH:5]=[CH:4][NH:3][C:2](=[O:31])[C:7]=1[C:8]1[NH:12][C:11]2[CH:13]=[C:14]([N:18]3[CH2:22][CH2:21][C:20]4([CH2:26][CH2:25][N:24]([CH2:27][CH3:28])[CH2:23]4)[CH2:19]3)[CH:15]=[C:16]([CH3:17])[C:10]=2[N:9]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a suspension of 2-(2-chloro-4-iodo-pyridin-3-yl)-6-(7-ethyl-2,7-diaza-spiro[4.4]non-2-yl)-4-methyl-1H-benzoimidazole (450 mg, 0.86 mmol) in H2O (1.5 mL) was added a solution of HCl in dioxane (4 M, 20 mL, 80 mmol). After it was heated at 85° C. for 5 h, the reaction mixture was evaporated to dryness under reduced pressure. The residue was purified by chromatography (100:10:1 CH2Cl2/MeOH/28% aqueous NH4OH) to afford the title compound (53 mg, 15%). 1H NMR (MeOH-d4) δ 1.18 (t, J=8 Hz, 3H), 1.87-2.07 (4H), 2.54 (s, 3H), 2.60-2.91 (6H), 3.19-3.39 (4H), 6.46 (s, 1H), 6.50 (s, 1H), 6.57 (d, J=6 Hz, 1H), 7.51 (d, J=6 Hz, 1H). ESI-MS m/z 412 (MH+).

Workup

customthe reaction mixture was evaporated to dryness under reduced pressure
customThe residue was purified by chromatography (100:10:1 CH2Cl2/MeOH/28% aqueous NH4OH)

Sources & evidence

ORD record: ord-5c132d5144b84242925510a82168437d
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629147B2

Reaction notes

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