Ammonium formate → 2-[4-(6-fluoro-1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide

HRID 914664Notes

Reaction equation

HRID 914664 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[C:12]3[C:21]4[N:17]([C:18]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)=[N:19][N:20]=4)[C:16]4[CH:28]=[CH:29][CH:30]=[CH:31][C:15]=4[N:14]([CH2:32][C:33]([N:35]([CH:44]([CH3:46])[CH3:45])[C:36]4[CH:37]=[N:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=4)=[O:34])[C:13]3=[O:47])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C([O-])=O.[NH4+]>CO.[Pd]>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:11][CH:12]3[C:21]4[N:17]([C:18]([C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=5)=[N:19][N:20]=4)[C:16]4[CH:28]=[CH:29][CH:30]=[CH:31][C:15]=4[N:14]([CH2:32][C:33]([N:35]([CH:44]([CH3:45])[CH3:46])[C:36]4[CH:37]=[N:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=4)=[O:34])[C:13]3=[O:47])=[CH:7][NH:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 1363477452-[4-(6-fluoro-1H-indol-3-ylmethylene)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide

Product 1

HCID 236604992-[4-(6-fluoro-1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamideYield 69.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 2-[4-(6-fluoro-1H-indol-3-ylmethylene)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide (158 mg, 0.252 mmol) in MeOH (20 mL) was added ammonium formate (463 mg, 7.34 mmol) and 10% palladium on charcoal (112 mg). The reaction was heated at reflux for 24 hours. The suspension was filtered hot, rinsing with 10% MeOH in CH2Cl2 (3×) and with CH2Cl2 (3×). The combined organic filtrates were concentrated and the residue was purified by medium pressure chromatography eluting with a solvent gradient (2% MeOH in CH2Cl2 to 8% MeOH in CH2Cl2) to yield 110 mg of 2-[4-(6-fluoro-1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide. 1H NMR (CD3OD) δ 8.08 (d, 1H), 7.39-7.62 (m, 9H) 7.15 (m, 2H), 6.93 (m, 3H), 6.68 (m, 1H), 4.80 (m, 1H), 4.55 (m, 1H), 4.20 (m, 1H), 3.95 (s, 3H), 3.88 (t, 1H), 3.77 (m, 1H), 3.67 (m, 1H), 1.01 (m, 6H); MS 630 (M+1), 628.5 (M−1).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 24 hours
  3. filtrationThe suspension was filtered hot
  4. washrinsing with 10% MeOH in CH2Cl2 (3×) and with CH2Cl2 (3×)
  5. concentrationThe combined organic filtrates were concentrated
  6. customthe residue was purified by medium pressure chromatography
  7. washeluting with a solvent gradient (2% MeOH in CH2Cl2 to 8% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-7dd8475cd7d74424be88858d1b6caa11
Source dataset
uspto-grants-2007_09
Patent number
US07265104B2

Reaction notes

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