Dimethylformamide → HCID 69223440, compound

HRID 2117268Notes

Reaction equation

HRID 2117268 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[O:11]=[C:12]1[C:18](=COS(C)(=O)=O)[C:17](=[O:25])[N:16]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:15]=[CH:14][N:13]1[CH2:32][C:33]([N:35]([CH:44]([CH3:46])[CH3:45])[C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1)=[O:34].[CH3:47][N:48]([CH:50]=[O:51])[CH3:49]>>[O:11]=[C:12]1[C:18](=[CH:47][N:48]2[C:49]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[NH:16][C:50]2=[O:51])[C:17](=[O:25])[N:16]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:15]=[CH:14][N:13]1[CH2:32][C:33]([N:35]([CH:44]([CH3:46])[CH3:45])[C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1)=[O:34]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 76540325HCID 76540325, compound

Product 1

HCID 69223440HCID 69223440, compound

Procedure

A solution of benzoximidazole (10.4 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 2-[2,4-dioxo-3-(methanesulfonyloxymethylene)-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)acetamide [containing approximately 40% of 2-[2,4-dioxo-3-methylene-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)acetamide](12s, 20mg). The reaction was allowed to warm to ambient temperature and stir overnight. Addition sodium bis(trimethylsilyl)amide (0.6 M in toluene, 129 μL) was added via micropipette. 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 1N NaHSO4. The layers were separated and the aqueous layer was back-extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered and evaporated in vacuo. The residue was purified on a preparative TLC plate (20×20 cm, 500 μM) 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-[2,4-dioxo-3-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)methylene-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)acetamide (10 mg) as a white lyophilate. 1H NMR (400 MHz, CDCI3) 0.99 (m, 6H), 3.62 (d, J=16 Hz, 1H), 3.79 (s, 3H), 4.10 (d, J=16 Hz, 1H), 4.23 (t, J=6 Hz, 1H), 4.50 (m, 2H), 4.90 (m, 1H), 5.86 (d, J=6 Hz, 1H), 5.91 (d, J=6 Hz, 1H), 6.99 (m, 7H), 7.26 (m, 3H), 7.33 (m, 2H), 7.46 (d, J=8 Hz, 1H), 7.54 (s, 1H).

Workup

  1. additionwas added via micropipette
  2. waitAfter approximately 10 min.
  3. customthe reaction mixture was quenched with several drops of glacial acetic acid
  4. customevaporated in vacuo
  5. customThe residue was partitioned between ethyl acetate and aqueous 1N NaHSO4
  6. customThe layers were separated
  7. extractionthe aqueous layer was back-extracted with ethyl acetate
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customThe residue was purified on a preparative TLC plate (20×20 cm, 500 μM)
  13. washeluting with 5% methanol in CH2Cl2
  14. customThe product band was removed
  15. washeluted with 4:1 CH2Cl2/methanol
  16. filtrationfiltered
  17. customevaporated in vacuo

Sources & evidence

ORD record
ord-f58d50640df846de85bb5a2ef8fae7d6
Source dataset
uspto-grants-2008_10
Patent number
US07442693B2

Reaction notes

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