Sodium bis(trimethylsilyl)amide → 3-[1-(tert-Butyl-phenyl-carbamoylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5,-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylmethyl]-indazole-1-carboxylic acid tert-butyl ester

HRID 343150Notes

Reaction equation

HRID 343150 reaction equation
C([N:5](C1C=CC=CC=1)[C:6](=[O:27])[CH2:7][N:8]1[C:14](=[O:15])[CH2:13][C:12](=[O:16])[N:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:10]2[CH:23]=[CH:24][CH:25]=[CH:26][C:9]1=2)(C)(C)C.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:45][C:46]1[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[N:48]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[N:47]=1>C1COCC1>[C:58]([O:57][C:55]([N:48]1[C:49]2[C:54](=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:46]([CH2:45][CH:13]2[C:14](=[O:15])[N:8]([C:7]([C:58]([CH3:61])([CH3:60])[CH3:59])([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C:6](=[O:27])[NH2:5])[C:9]3[CH:26]=[CH:25][CH:24]=[CH:23][C:10]=3[N:11]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:12]2=[O:16])=[N:47]1)=[O:56])([CH3:61])([CH3:60])[CH3:59]

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 10789281N-tert-Butyl-2-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-phenyl-acetamideHCID 108049513-(Bromomethyl)-1H-indazole, N1-BOC protected

Product 1

HCID 676968193-[1-(tert-Butyl-phenyl-carbamoylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5,-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylmethyl]-indazole-1-carboxylic acid tert-butyl esterYield 64.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred slurry of 514 mg (1.17 mmol) N-tert-Butyl-2-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-phenyl-acetamide, prepared as in Part B, in 15 mL THF cooled to 0° C. is added 1.28 mL (1.28 mmol, 1.1 equiv) of 1M Sodium bis(trimethylsilyl)amide in THF at ambient temperature and stirred 0.5 h. To this solution is added 381 mg (1.22 mmol, 1.05 equiv) 3-bromomethyl-1-tert-butoxycarbonyl-1H-indazole and the resultant reaction mixture stirred 1 h at 0° C. followed by 18 h at ambient temperature. The solvent is removed in vacuo and the residue taken into EtOAc (50 mL), washed with H2O (30 mL) and brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product is purified by flash chromatography on 20 g silica gel eluted with EtOAc/Hexanes (1:3, 350 mL). Appropriate fractions were combined and concentrated in vacuo to give 263 mg (0.392 mmol) of the title compound as a white foam: 1H NMR (CDCl3, 300 MHz) δ8.04 (d, 1H, J=8.4), 7.89 (d, 1H, J=7.9), 7.51-7.20 (m, 14H), 7.10 (m, 1H), 6.94 (m, 1H), 4.28 (m, 1H), 4.20-4.06 (m, 2H), 3.84 (m, 1H), 3.56 (m,1H), 1.66 (s, 9H), 1.39 (s, 9H); TLC Rf =0.16 (EtOAc/Hexanes, 1:3).

Workup

  1. customthe resultant reaction mixture
  2. stirringstirred 1 h at 0° C.
  3. waitfollowed by 18 h at ambient temperature
  4. customThe solvent is removed in vacuo
  5. washwashed with H2O (30 mL) and brine (30 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product is purified by flash chromatography on 20 g silica gel
  10. washeluted with EtOAc/Hexanes (1:3, 350 mL)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-60286b7c50b74ab9b9bb72b59ed9f941
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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