Formic Acid → 2-[2,4-Dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1H-indazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

HRID 343222Notes

Reaction equation

HRID 343222 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:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:4](=[O:34])[CH:3]1[CH2:35][C:36]1[C:44]2[CH2:43][CH2:42][CH2:41][CH2:40][C:39]=2[N:38](CC2C=CC=CC=2)[N:37]=1.C(O)=O>C(O)C.[Pd]>[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:22])[CH3:23])[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:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:4](=[O:34])[CH:3]1[CH2:35][C:36]1[C:44]2[CH2:43][CH2:42][CH2:41][CH2:40][C:39]=2[NH:38][N:37]=1

Participants

5

Reactant 2

HCID 284Formic AcidHCID 106045852-[2,4-Dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1-benzyl-1H-indazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

Product 1

HCID 108172412-[2,4-Dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1H-indazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamideYield 80.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a stirring solution of 150 mg (0.22 mmol) of 2-[2,4-Dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1-benzyl-1H-indazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Intermediate 52, in 10 mL of a 10% solution of formic acid in absolute ethanol is added 150 mg of 10% palladium on carbon. The resulting black suspension is refluxed for 3 h, then cooled to RT. The reaction mixture is filtered through Celite to remove the catalyst and the solvent removed in vacuo. Purification of the residue via silica gel MPLC using an Si60 column and hexane/EtOAc 1/5 as eluent afforded 105 mg of the title compound as a white solid: mp 170°-173° C.; 1H NMR (CDCl3, 400 MHz) δ7.38-6.88 (m, 13H), 5.03 (m, 1H), 4.34 (d, 1H, J=16.8), 4.14 (d, 1H, J=16.8), 3.84(s, 3H), 3.58 (dd, 1H, J=6.8, 6.8), 3.46 (dd, 1H, J=7.0, 14.0), 3.30 (dd, 1H, J=7.5, 15.2), 2.60 (m, 2H), 2.36 (m, 2H), 1.70 (m, 4H), 1.08 (2×d, 6H, J=6.6); low resolution MS (FAB)m/e 592 (MH+), 591 (M+), 427; Anal. (C35H37N5O4) Calcd. C, 71.05; H, 6.30; N, 11.84; Found C, 70.20; H, 6.47; N, 11.66.

Workup

  1. temperatureThe resulting black suspension is refluxed for 3 h
  2. filtrationThe reaction mixture is filtered through Celite
  3. customto remove the catalyst
  4. customthe solvent removed in vacuo
  5. customPurification of the residue via silica gel MPLC

Sources & evidence

ORD record
ord-e5651b9f3b15467497dda4dec420d3c2
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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