Formic Acid → HCID 178492389, compound

HRID 343223Notes

Reaction equation

HRID 343223 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([O:52][CH3:53])[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]=[N:47][CH:48]=[CH:49][CH:50]=3)[C:19]2=[O:51])=[N:9]1)C1C=CC=CC=1.C(O)=O>[Cl-].[Na+].O.C(OCC)(=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([O:52][CH3:53])[C:24](=[O:25])[N:23]([CH2:26][C:27]([N:29]([CH:38]([CH3:40])[CH3:39])[C:30]3[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)=[O:28])[C:22]3[CH:41]=[CH:42][CH:43]=[CH:44][C:21]=3[N:20]([C:45]3[CH:46]=[N:47][CH:48]=[CH:49][CH:50]=3)[C:19]2=[O:51])=[N:9]1

Participants

5

Reactant 2

HCID 284Formic AcidHCID 676968152-[3-(1-Benzyl-1H-indazol-3-ylmethyl)-3-methoxy-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

Product 1

HCID 178492389HCID 178492389, compoundYield 54.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 131718255Brine ethyl acetateSolvent

Procedure

To a stirring solution of 350 mg (0.49 mmol) of 2-[3-(1-Benzyl-1H-indazol-3-ylmethyl)-3-methoxy-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Intermediate 55, in a 10 mL solution of 5% formic acid (v/v) in absolute ethanol/DMF 1/1 is added 350 mg of 10% palladium on carbon. The resulting mixture is heated to reflux for 3 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 flash column chromatography using hexane/EtOAc 1/2 as eluent afforded 166 mg of the title compound as a white solid: mp 207°-209° C.; 1H NMR (CDCl3, 400 MHz) δ10.05 (s, br, 1H), 8.43 (d, 1H, J=4.6), 8.29 (s, 1H), 7.94 (d, 1H, J=8.2), 7.56 (d, 1H, J=7.2), 7.39 (d, 1H, J=7.8), 7.29 (m, 2H), 7.25-7.09 (m, 5H), 6.98 (m, 3H), 6.65 (d, 1H, J=8.1), 5.06 (m, 1H), 4.25 (dd, 2H, J=16.0, 198.0), 4.07 (dd, 2H, J=16.2, 107.8), 3.84 (s, 3H), 3.21 (s, 3H), 1.12 (2×d, 6H, J=7.2); low resolution MS (FAB)m/e 619 (MH+), 618 (M+); Anal. (C35H34N6O5) Calcd. C, 67.95; H, 5.54; N, 13.58 Found C, 67.85; H, 5.51; N, 13.59.

Workup

  1. temperatureThe resulting mixture is heated
  2. temperatureto reflux for 3 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 flash column chromatography

Sources & evidence

ORD record
ord-eb5b9c7efa414651b223a616313db39f
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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