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

HRID 470309Notes

Reaction equation

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

Participants

Conditions

Temperature: 85 °C

Procedure

To a suspension of 2-[2-(2-chloro-4-iodo-pyridin-3-yl)-7-methyl-3H-benzoimidazol-5-yl]-2,8-diaza-spiro[5.5]undecane (144 mg, 0.28 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 18 h, the reaction mixture was evaporated to dryness under reduced pressure. The residue was purified by chromatography (50:10:1 CH2Cl2/MeOH/28% aqueous NH4OH) to afford the title compound (16 mg, 27%). 1H NMR (MeOH-d4) δ 1.35-1.82 (8H), 2.54 (s, 3H), 2.90-3.19 (8H), 6.60 (d, J=7 Hz, 1H), 6.89 (s, 1H), 6.96 (s, 1H), 7.58 (d, J=7 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 (50:10:1 CH2Cl2/MeOH/28% aqueous NH4OH)

Sources & evidence

ORD record: ord-32368d110bcf43a0ae84e286cd10ea4d
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629147B2

Reaction notes

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