2-[3-(2-Benzyl-5-methyl-2H-pyrazol-3ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide → HCID 178492378, compound

HRID 343225Notes

Reaction equation

HRID 343225 reaction equation
C([N:8]1[C:12]([CH2:13][CH:14]2[C:20](=[O:21])[N:19]([CH2:22][C:23]([N:25]([CH:34]([CH3:36])[CH3:35])[C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)=[O:24])[C:18]3[CH:37]=[CH:38][CH:39]=[CH:40][C:17]=3[N:16]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:15]2=[O:47])=[CH:11][C:10]([CH3:48])=[N:9]1)C1C=CC=CC=1>C(O)=O.C(O)C.[Pd]>[CH:34]([N:25]([C:26]1[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=1)[C:23](=[O:24])[CH2:22][N:19]1[C:20](=[O:21])[CH:14]([CH2:13][C:12]2[NH:8][N:9]=[C:10]([CH3:48])[CH:11]=2)[C:15](=[O:47])[N:16]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:17]2[CH:40]=[CH:39][CH:38]=[CH:37][C:18]1=2)([CH3:35])[CH3:36]

Participants

5

Reactant 1

HCID 867536032-[3-(2-Benzyl-5-methyl-2H-pyrazol-3ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

Product 1

HCID 178492378HCID 178492378, compoundYield 67.7%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 284Formic AcidSolventHCID 702EthanolSolvent

Procedure

To a stirring solution of 194 mg (0.30 mmol) of 2-[3-(2-Benzyl-5-methyl-2H-pyrazol-3ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Example 54, in 10 mL of 5% formic acid (v/v) in absolute ethanol is added 190 mg of 10% palladium on carbon. The resulting mixture is heated to reflux for 2 h, then cooled to RT and filtered through a pad of Celite to remove the catalyst. The filtrate is concentrated, then poured into 50 mL of EtOAc and washed successively with 1N NaOH (1×50 mL) and H2O (1×50 mL). The organic layer is separated, dried (MgSO4), and the solvents removed in vacuo. Purification by silica gel MPLC using EtOAc/chloroform 8/1 as eluent afforded 112 mg of the title compound as a white solid: mp 156°-159° C.; 1H NMR (CDCl3, 400 MHz) δ7.38-7.18 (m, 9H), 7.14 (d, 1H, J=8.7), 7.06 (t, 1H, J=7.3), 6.96 (m, 2H), 6.86 (d, 1H, J=7.6), 5.81 (s, 1H), 5.02 (m, 1H), 4.18 (dd, 2H, J=16.5, 86.1), 3.83 (s, 3H), 3.59 (t, 1H, J=6.8), 3.32 (ddd, 2H, J=7.5, 15.2, 34.3), 2.19 (s, 3H), 1.08 (m, 6H); low resolution MS (FAB)m/e 552 (MH+), 551 (M+), 387; Anal. (C32H33N5O4) Calcd. C, 69.67; H, 6.03; N, 12.70 Found C, 69.61; H, 6.11; N, 12.44.

Workup

  1. temperatureThe resulting mixture is heated
  2. temperatureto reflux for 2 h
  3. filtrationfiltered through a pad of Celite
  4. customto remove the catalyst
  5. concentrationThe filtrate is concentrated
  6. additionpoured into 50 mL of EtOAc
  7. washwashed successively with 1N NaOH (1×50 mL) and H2O (1×50 mL)
  8. customThe organic layer is separated
  9. dry with materialdried (MgSO4)
  10. customthe solvents removed in vacuo
  11. customPurification by silica gel MPLC

Sources & evidence

ORD record
ord-595a9388aa7940828d646eecc9dc825e
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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