Diisopropylethylamine → Benzimidazole

HRID 900058

Reaction equation

HRID 900058 reaction equation
C1NC2N([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)C=NC=2C(=S)N=1.[N:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[NH:22][CH:21]=1.CO.[I-].C(C[P+](C)(C)C)#N.C(N(C(C)C)CC)(C)C>C(#N)CC.O>[N:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[NH:22][CH:21]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 6761666-ThioinosineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 23299442Benzimidazole methyl alcohol

Product 1

HCID 5798Benzimidazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7854PropionitrileSolvent

Procedure

Benzimidazole analogs were synthesized by a Mitsunobu coupling (Zaragoza, F. Tetrahedron 2001, 57, 5451-5454 and Zaragoza, F.; Stephensen, H. J. Org. Chem. 2001, 66, 2518-2521) of 6-mercaptopurine riboside with benzimidazole-methyl alcohol (Kimura, T.; Takase, Y.; Hayashi, K.; Tanaka, H.; Ohtsuka, I.; Saeki, T.; Kogushi, M.; Yamada, T.; Fujimori, T.; Saitou, I.; Akasaka, K. J. Med. Chem. 1993, 36, 1630-1640), in the presence of (cyanomethyl)trimethylphosphonium iodide (36) and diisopropylethylamine (DIPEA) in propionitrile (Scheme 4). After refluxing of this mixture for 18 hr, water was added and the product precipitated. The direct use of alcohol 34 and 35 is an advantage of this method compared to the previous reactions. (Temple, C.; Kussner, C. L.; Montgomery, J. A. J. Org. Chem. 1968, 11, 41-43). These alcohols were prepared from reduction of the appropriate esters via standard procedures. (Sun, Q.; Gatto, B.; Yu, C.; Liu, A.; Liu, L. F.; LaVoie, E. J. J. Med. Chem. 1995, 38, 3638-3644).

Workup

  1. temperatureAfter refluxing of this mixture for 18 hr
  2. customthe product precipitated

Sources & evidence

ORD record
ord-d84d97087def468da7fdf9b39d5854c5
Source dataset
uspto-grants-2008_04
Patent number
US07358235B2

Linked notes

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