Pyridine → HCID 73174711, compound

HRID 503210Notes

Reaction equation

HRID 503210 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][O:8][CH2:9][C:10]1[CH:11]=[C:12]([N:16]2[C:20]3[CH:21]=[CH:22][C:23]([CH:25]=O)=[CH:24][C:19]=3[N:18]=[CH:17]2)[CH:13]=[CH:14][CH:15]=1.N1C=CC=CC=1.Cl.[NH2:34][OH:35]>C(O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][O:8][CH2:9][C:10]1[CH:11]=[C:12]([N:16]2[C:20]3[CH:21]=[CH:22][C:23]([CH:25]=[N:34][OH:35])=[CH:24][C:19]=3[N:18]=[CH:17]2)[CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 443297Hydroxyamine hydrochlorideHCID 57556918HCID 57556918, compound

Product 1

HCID 73174711HCID 73174711, compoundYield 78.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of compound 12a (220 mg, 0.64 mmol) and pyridine (0.08 mL, 1.5 equiv) in ethanol (2 mL) was added hydroxylamine hydrochloride (500 mg) and the reaction mixture was stirred at RT for 3 hours. The reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (100 mL), washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel using a mixture of ethyl acetate and pet-ether as the eluent to afford compound 14a (180 mg, 78%) as a solid. Mp 154-154.8° C. In analogy herewith, the following compounds were prepared: 1-[3-(1-Methyl-1H-imidazol-2-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14b) from 12b. Mp 209.8-211.7° C. and 1-[3-(2-Methyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14c) from 12c. Mp 145.8-147.7° C. O-Methyl 1-[3-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14h) from 12c and O-methyl hydroxylamine. LC-ESI-HRMS of [M+H]+ shows 377.1724 Da. Calc. 377.172525 Da, dev. −0.3 ppm 1-[3-(2-Methyl-2H-pyrazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14e) from 12e. LC-ESI-HRMS of [M+H]+ shows 362.1603 Da. Calc. 362.161625 Da, dev. −3.7 ppm O-Methyl 1-[3-(2-methyl-2H-pyrazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14i) from 12e and O-methyl hydroxyl amine. LC-ESI-HRMS of [M+H]+ shows 376.1755 Da. Calc. 376.177325 Da, dev. −4:9 ppm 1-[3-(1,3-Thiazol-2-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14j) from 12g. LC-ESI-HRMS of [M+H]+ shows 365.1074 Da. Calc. 365.107225 Da, dev. 0.5 ppm O-Methyl 1-[3-(1,3-thiazol-2-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14g) from 12g and O-methyl hydroxylamine. LC-ESI-HRMS of [M+H]+ shows 379.1238 Da. Calc. 379.122825 Da, dev. 2.6 ppm and 1-[3-(Pyridin-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14d) 1-[3-(Pyrimidin-4-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14f) are prepared likewise.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate (100 mL)
  3. washwashed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography on silica gel using
  7. additiona mixture of ethyl acetate and pet-ether as the eluent

Sources & evidence

ORD record
ord-d62e43e24e174c6abf05a2ee9aa34bcb
Source dataset
uspto-grants-2010_08
Patent number
US07776900B2

Reaction notes

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