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

HRID 343136Notes

Reaction equation

HRID 343136 reaction equation
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:28]2[CH:32]=[CH:31][S:30][CH:29]=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]([CH:21]([CH3:23])[CH3:22])[C:13]3[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=3)=[O:11])[C:7]3[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=3[N:5]([C:28]3[CH:32]=[CH:31][S:30][CH:29]=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 108049513-(Bromomethyl)-1H-indazole, N1-BOC protectedHCID 21584169Diethylether ethylacetateHCID 676963452-(2,4-dioxo-5-thiophen-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

Product 1

HCID 676963882-[3-(1-tert-butoxycarbonyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-thiophen-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamideYield 106.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 340 mg (0.80 mmol) of 2-(2,4-dioxo-5-thiophen-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Part A, in 10 mL DMF at 0° C. is added 1.93 mL (0.96 mmol, 1.2 equiv) of NaN(TMS)2 in toluene. The resulting solution is stirred 5 min and 299 mg (0.96 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 590 mg of the crude title compound: low resolution MS (FAB) m/e 694 (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-d36453e6329d41f984bd00579ea455c0
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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