Sodium bis(trimethylsilyl)amide → HCID 69223435, compound

HRID 2117265Notes

Reaction equation

HRID 2117265 reaction equation
[O:1]=[C:2]1[CH2:8][C:7](=[O:9])[N:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]1[CH2:16][C:17]([N:19]([CH:28]([CH3:30])[CH3:29])[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)=[O:18].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:41][Si:42]([CH3:50])([CH3:49])[O:43][CH2:44][CH2:45][O:46][CH2:47]Cl>CN(C=O)C>[O:1]=[C:2]1[C:8](=[CH:47][O:46][CH2:45][CH2:44][O:43][Si:42]([CH3:50])([CH3:49])[CH3:41])[C:7](=[O:9])[N:6]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:5]=[CH:4][N:3]1[CH2:16][C:17]([N:19]([CH:28]([CH3:30])[CH3:29])[C:20]1[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=1)=[O:18]

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 14107261HCID 14107261, compoundHCID 57446292HCID 57446292, compound

Product 1

HCID 69223435HCID 69223435, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl)-N-isopropyl-N-(4-methoxyphenyl)acetamide (12p, 1.500 g) in anhydrous DMF (15 mL) under argon was cooled to 0-5° C. Sodium bis(trimethylsilyl)amide (0.6 M in toluene, 7.68 mL) was added via syringe followed 5 minutes later by chloromethyl 2-(trimethylsilyloxy)-1-ethyl ether (0.815 mL). After approximately 10 min., the reaction was quenched with glacial acetic acid and evaporated in vacuo. The residue was partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was back-extracted twice with ethyl acetate. The combined organic layers were dried over anhydrous MgSO4, filtered and evaporated in vacuo. The crude product was purified on flash grade silica gel eluting with 2:5 ethyl acetate/hexane. Fractions containing the product were combined, evaporated in vacuo and dried under high vacuum to provide 2-[2,4-dioxo-5-phenyl-3-[2-(trimethylsilyloxy)-1-ethoxymethylene]-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)acetamide(12q, 1.236 g) as a foam. 1H NMR (400 MHz, CDCl3) 0.00 (s, 9H), 0.95 (m, 2H), 1.04 (d, J=6 Hz, 3H), 1.06 (d, J=6 Hz, 3H), 3.62 (m, 3H), 3.83 (s, 3H), 3.91 (d, J=2 Hz, 2H), 4.02 (dd, J=5,10Hz, 1H), 4.15 (dd, J=8,10Hz, 1H), 4.95 (m, 1H), 5.93 (d, J=6 Hz, 1H), 5.99 (d, J=6 Hz, 1H), 6.94 (m, 2H), 7.11 (m, 2H), 7.33 (m, 5H).

Workup

  1. customthe reaction was quenched with glacial acetic acid
  2. customevaporated in vacuo
  3. customThe residue was partitioned between ethyl acetate and water
  4. customThe layers were separated
  5. extractionthe aqueous layer was back-extracted twice with ethyl acetate
  6. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude product was purified on flash grade silica gel eluting with 2:5 ethyl acetate/hexane
  10. additionFractions containing the product
  11. customevaporated in vacuo
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-b6604c2215e74f01b8fa1a2e73492450
Source dataset
uspto-grants-2008_10
Patent number
US07442693B2

Reaction notes

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