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 → HCID 178449516, compound

HRID 343230Notes

Reaction equation

HRID 343230 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH:18]2[C:24](=[O:25])[N:23]([C:26](C(C)(C)C)(C3C=CC=CC=3)[C:27](=[O:29])[NH2:28])[C:22]3[CH:40]=[CH:41][CH:42]=[CH:43][C:21]=3[N:20]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:19]2=[O:50])=[N:9]1)=O)(C)(C)C>Cl.O1CCOCC1>[C:18]([N:28]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:27](=[O:29])[CH2:26][N:23]1[C:24](=[O:25])[CH:18]([CH2:17][C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[NH:8][N:9]=2)[C:19](=[O:50])[N:20]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:40]2[CH:41]=[CH:42][CH:43]=[CH:21][C:22]1=2)([CH3:24])([CH3:19])[CH3:17]

Participants

4

Reactant 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 ester

Product 1

HCID 178449516HCID 178449516, compoundYield 57.7%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

263 mg (0.392 mmol) 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, prepared as in Intermediate 65, is dissolved in 3 mL 4N HCl in Dioxane and stirred 1 h at ambient temperature. The solvent is removed in vacuo and the residue taken into EtOAc (50 mL), washed with satd. NaHCO3 (30 mL) and brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product is purified by flash chromatography on 5 g silica gel eluted successively with EtOAc/Hexanes (1:2, 50 mL), (2:3, 80 mL), (1:1, 50 mL). Appropriate fractions were combined and concentrated in vacuo to give 65 mg (0.113 mmol) of the title compound as a white foam: 1H NMR (CDCl3, 300 MHz) δ7.82 (d, 1H, J=7.5), 7.43-7.06 (m, 16H), 4.19 (m, 2H), 4.08 (m, 1H), 3.79 (m, 1H), 3.63 (m, 1H), 1.37 (s, 9H); low resolution MS (FAB) m/e 572.2 (MH+); TLC Rf =0.41 (EtOAc/Hexanes, 3:2).

Workup

  1. customThe solvent is removed in vacuo
  2. washwashed with satd
  3. dry with materialNaHCO3 (30 mL) and brine (30 mL), dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by flash chromatography on 5 g silica gel
  7. washeluted successively with EtOAc/Hexanes (1:2, 50 mL), (2:3, 80 mL), (1:1, 50 mL)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fb26bcd9c7444e11955fb937f7e54c8c
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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