Formic Acid → HCID 178492390, compound

HRID 343207Notes

Reaction equation

HRID 343207 reaction equation
C([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][C:18]2([CH3:52])[C:24](=[O:25])[N:23]([CH2:26][C:27]([N:29]([CH:38]([CH3:40])[CH3:39])[C:30]3[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=3)=[O:28])[C:22]3[CH:41]=[CH:42][CH:43]=[CH:44][C:21]=3[N:20]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[C:19]2=[O:51])=[N:9]1)C1C=CC=CC=1.C(O)=O>C(O)C.[Pd]>[NH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][C:18]2([CH3:52])[C:24](=[O:25])[N:23]([CH2:26][C:27]([N:29]([CH:38]([CH3:40])[CH3:39])[C:30]3[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=3)=[O:28])[C:22]3[CH:41]=[CH:42][CH:43]=[CH:44][C:21]=3[N:20]([C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=3)[C:19]2=[O:51])=[N:9]1

Participants

5

Reactant 2

HCID 284Formic AcidHCID 677001112-[3-(1-Benzyl-1H-indazol-3-ylmethyl)-3-methyl-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 178492390HCID 178492390, compoundYield 17.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a stirring solution of 190 mg (0.28 mmol) of 2-[3-(1-Benzyl-1H-indazol-3-ylmethyl)-3-methyl-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 Intermediate 39, in 15 mL of a 10% solution of formic acid in absolute ethanol is added 200 mg of 10% palladium on carbon. The resulting black suspension is heated at reflux for 6 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 by silica gel flash column chromatography using hexane/EtOAc 3/2 as eluent followed by further purification via silica gel MPLC using an Si60 column and hexane/EtOAc 2/1 as eluent and lyophilization afforded 30 mg of the title compound as a white amorphous solid: 1H NMR (DMSO-d6, 300 MHz) δ7.48-6.98 (m, 17H), 6.70 (d, 1H, J=7.8), 4.86 (m, 1H), 4.27 (m, 2H), 3.81 (s, 3H), 2.87 (dd, 2H), 1.29 (s, 3H), 1.00 (m, 6H); low resolution MS (FAB)m/e 602 (MH+), 437, 279, 223.

Workup

  1. temperatureThe resulting black suspension is heated
  2. temperatureat reflux for 6 h
  3. filtrationThe reaction mixture is filtered through Celite
  4. customto remove the catalyst
  5. customthe solvent removed in vacuo
  6. customPurification of the residue by silica gel flash column chromatography
  7. customfollowed by further purification via silica gel MPLC

Sources & evidence

ORD record
ord-ac0c64b5d94d4480ad783906fa6e75ae
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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