Sodium bis(trimethylsilyl)amide → 2-[3-(1-tert-butoxycarbonyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-(4-fluoro-phenyl)-N-isopropyl-acetamide

HRID 343135Notes

Reaction equation

HRID 343135 reaction equation
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH:13]([CH3:15])[CH3:14])=[O:11])[C:7]2[CH:23]=[CH:24][CH:25]=[CH:26][C:6]=2[N:5]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:4](=[O:33])[CH2:3]1.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.CCOCC.CCOC(C)=O>CN(C=O)C.C1(C)C=CC=CC=1>[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:3]2[C:2](=[O:1])[N:8]([CH2:9][C:10]([N:12]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:13]([CH3:15])[CH3:14])=[O:11])[C:7]3[CH:23]=[CH:24][CH:25]=[CH:26][C:6]=3[N:5]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:4]2=[O:33])=[N:47]1)=[O:56])([CH3:61])([CH3:60])[CH3:59]

Participants

7

Reactant 4

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 105513202-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-(4-fluoro-phenyl)-N-isopropyl-acetamideHCID 108049513-(Bromomethyl)-1H-indazole, N1-BOC protectedHCID 21584169Diethylether ethylacetate

Product 1

HCID 105803742-[3-(1-tert-butoxycarbonyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-(4-fluoro-phenyl)-N-isopropyl-acetamideYield 117.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 500 mg (1.12 mmol) of 2-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-(4-fluoro-phenyl)-N-isopropyl-acetamide, prepared as in Part B, in 10 mL DMF at 0° C. is added 2.68 mL (1.34 mmol, 1.2 equiv) of NaN(TMS)2 in toluene. The resulting solution is stirred 5 min, and 417 mg (1.34 mmol, 1.2 equiv) of 3-bromomethyl-1-tert-butoxycarbonyl-1H-indazole is added. The resulting solution is stirred 4.5 h, poured into 100 mL Et2O/EtOAc (1:1), washed with H2O (2×50 mL). The organic layer is separated, dried (MgSO4), and the solvents removed in vacuo to afford 890 mg of the crude title compound: low resolution MS (FAB) m/e 676 (MH+).

Workup

  1. stirringThe resulting solution is stirred 4.5 h
  2. washwashed with H2O (2×50 mL)
  3. customThe organic layer is separated
  4. dry with materialdried (MgSO4)
  5. customthe solvents removed in vacuo

Sources & evidence

ORD record
ord-925e033f53b84c60b22768e6d32fad28
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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