Iodine → 2-(4-Iodo-2-methoxy-pyridin-3-yl)-7-methyl-3H-benzimidazole-5-carbonitrile

HRID 1354606Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH3:11])[C:9]=1[NH2:10])[C:5]#[N:6].[I:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([O:19][CH3:20])[C:14]=1[CH:21]=O.II>CO>[I:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([O:19][CH3:20])[C:14]=1[C:21]1[NH:1][C:2]2[CH:3]=[C:4]([C:5]#[N:6])[CH:7]=[C:8]([CH3:11])[C:9]=2[N:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3,4-diamino-5-methyl-benzonitrile (2.00 g, 13.6 mmol) in MeOH (40 mL) was added 4-iodo-2-methoxy-pyridine-3-carbaldehyde (3.6 g, 13.6 mmol) in MeOH (20 mL) at 0° C. The resulting slurry was stirred at 0° C. for 1 h. Iodine (1.73 g, 8.8 mmol) in MeOH (10 mL) was added dropwise via a dropping funnel to the reaction mixture at 0° C. The reaction mixture was stirred at room temperature for 14 h. After removal of MeOH, the residue was diluted with saturated Na2S2O3 and extracted with EtOAc. The combined organic layers were washed with water and brine, dried over Na2SO4. The crude product was purified by flash column chromatography (3% MeOH/CH2Cl2) to yield the title compound (1.81 g, 46%). 1H NMR (300 MHz, CDCl3) δ 7.90 (1H, s), 7.49 (1H, d, J=5.4 Hz), 7.46 (1H, s), 7.41 (1H, d, J=5.3 Hz), 3.78 (3H, s), 2.68 (3H, s). LCMS (M+H)+ m/z 391 (t=1.27 min.).

Workup

stirringThe reaction mixture was stirred at room temperature for 14 h
customAfter removal of MeOH
additionthe residue was diluted with saturated Na2S2O3
extractionextracted with EtOAc
washThe combined organic layers were washed with water and brine
dry with materialdried over Na2SO4
customThe crude product was purified by flash column chromatography (3% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-d929c22fa4e74378921d8b828fce5bb3
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07223757B2

Reaction notes

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