Hydrochloric Acid → 3-[6-(8-benzyl-2,8-diaza-spiro[5.5]undec-2-yl)-4-methyl-1H-benzoimidazol-2-yl]-4-chloro-1H-pyridin-2-one

HRID 470308Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]2([CH2:18][CH2:17][CH2:16][N:15]([C:19]3[CH:35]=[C:34]([CH3:36])[C:22]4[N:23]=[C:24]([C:26]5[C:27](Cl)=[N:28][CH:29]=[CH:30][C:31]=5I)[NH:25][C:21]=4[CH:20]=3)[CH2:14]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:37].[O:38]1CCOCC1>O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]2([CH2:14][N:15]([C:19]3[CH:35]=[C:34]([CH3:36])[C:22]4[N:23]=[C:24]([C:26]5[C:27](=[O:38])[NH:28][CH:29]=[CH:30][C:31]=5[Cl:37])[NH:25][C:21]=4[CH:20]=3)[CH2:16][CH2:17][CH2:18]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a suspension of 2-benzyl-8-[2-(2-chloro-4-iodo-pyridin-3-yl)-7-methyl-3H-benzoimidazol-5-yl]-2,8-diaza-spiro[5.5]undecane (55 mg, 0.09 mmol) in H2O (0.75 mL) was added a solution of HCl in dioxane (4 M, 10 mL, 40 mmol). After it was heated at 85° C. for 18 h, the reaction mixture was evaporated to dryness under reduced pressure. The residue was purified by chromatography (170:10:1 CH2Cl2/MeOH/28% aqueous NH4OH) to afford the title compound (17 mg, 38%). 1H NMR (MeOH-d4) δ 1.23-1.35 (2H), 1.50-1.72 (6H), 2.09-2.31 (2H), 2.55 (s, 3H), 2.58-2.65 (2H), 2.88-3.72 (6H), 6.60 (d, J=6 Hz, 1H), 6.83 (s, 1H), 7.19-7.32 (6H), 7.52 (d, J=6 Hz, 1H). ESI-MS m/z 502 (MH+).

Workup

customthe reaction mixture was evaporated to dryness under reduced pressure
customThe residue was purified by chromatography (170:10:1 CH2Cl2/MeOH/28% aqueous NH4OH)

Sources & evidence

ORD record: ord-7f8ec711c25d46d9a67610291e3bf308
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629147B2

Reaction notes

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