Benzimidazole → HCID 11512174, compound

HRID 2117270Notes

Reaction equation

HRID 2117270 reaction equation
[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].CS(O[CH2:25][CH:26]1[C:32](=[O:33])[N:31]([CH2:34][C:35]([N:37]([CH:46]([CH3:48])[CH3:47])[C:38]2[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=2)=[O:36])[CH:30]=[CH:29][N:28]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:27]1=[O:55])(=O)=O>CN(C=O)C>[N:1]1([CH2:25][CH:26]2[C:32](=[O:33])[N:31]([CH2:34][C:35]([N:37]([CH:46]([CH3:47])[CH3:48])[C:38]3[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=3)=[O:36])[CH:30]=[CH:29][N:28]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C:27]2=[O:55])[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

5

Reactant 3

HCID 5798BenzimidazoleHCID 2724254Sodium bis(trimethylsilyl)amideHCID 86616501HCID 86616501, compound

Product 1

HCID 11512174HCID 11512174, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of benzimidazole (9.2 mg) in anhydrous DMF (1.5 mL) under argon was cooled to 0-5° C. Sodium bis(trimethylsilyl)amide (0.6 M in toluene, 129 μL) was added via micropipette followed by (1-{2-[isopropyl(4-methoxyphenyl)amino]-2-oxoethyl}-5,7-dioxo-4-phenyl-4,5,6,7-tetrahydro-1H-1,4-diazepin-6-yl)methyl methanesulfonate (20 mg). After approximately 10 min., the reaction mixture was quenched with several drops of glacial acetic acid and evaporated in vacuo. The residue was partitioned between ethyl acetate and aqueous K2CO3 (5% w/v). The layers were separated and the aqueous layer was back-extracted with ethyl acetate. The combined organic layers were dried over anhydrous MgSO4, filtered and evaporated in vacuo. The residue was purified on a preparative TLC plate (20×20 cm, 500 □M) eluting with 5% methanol in CH2Cl2. The product band was removed, eluted with 4:1 CH2Cl2/methanol, filtered and evaporated in vacuo. The residue was lyophilized from CH3CN/H2O to provide 2-[6-(1H-benzimidazol-1-ylmethyl)-5,7-dioxo-4-phenyl-4,5,6,7-tetrahydro-1H-1,4-diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)acetamide as a white lyophilate (15 mg). 1H NMR (300 MHz, CDCl3) 1.13 (m, 6H), 3.86 (m, 1H), 3.90 (s, 3H), 3.97 (d, J=4 Hz, 2H), 4.90 (m, 1H), 5.07 (m, 2H), 5.90 (d, J=7 Hz, 1H), 5.99 (d, J=7 Hz, 1H), 7.01 (m, 2H), 7.18 (m, 2H), 7.33 (m, 8H), 7.85 (m, 1H), 8.26 (s, 1H).

Workup

  1. customthe reaction mixture was quenched with several drops of glacial acetic acid
  2. customevaporated in vacuo
  3. customThe residue was partitioned between ethyl acetate and aqueous K2CO3 (5% w/v)
  4. customThe layers were separated
  5. extractionthe aqueous layer was back-extracted with ethyl acetate
  6. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified on a preparative TLC plate (20×20 cm, 500 □M)
  10. washeluting with 5% methanol in CH2Cl2
  11. customThe product band was removed
  12. washeluted with 4:1 CH2Cl2/methanol
  13. filtrationfiltered
  14. customevaporated in vacuo

Sources & evidence

ORD record
ord-8142bae2c9ac4d9d8fcaec132682d7cc
Source dataset
uspto-grants-2008_10
Patent number
US07442693B2

Reaction notes

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