HCID 59352270, compound → HCID 59352354, compound

HRID 2385529Notes

Reaction equation

HRID 2385529 reaction equation
C([NH:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[C:11]1([C:41]3[C:32](=[CH:33][C:34]4[O:39][CH2:38][CH2:37][O:36][C:35]=4[CH:40]=3)[O:31][CH2:30]1)[C:12](=[O:29])[N:13]2[CH2:18][C:19]1[C:24]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:22]=[CH:21][N:20]=1)C1C=CC=CC=1>C(O)(=O)C.[OH-].[OH-].[Pd+2].CO>[NH2:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[C:11]1([C:41]3[C:32](=[CH:33][C:34]4[O:39][CH2:38][CH2:37][O:36][C:35]=4[CH:40]=3)[O:31][CH2:30]1)[C:12](=[O:29])[N:13]2[CH2:18][C:19]1[C:24]([C:25]([F:28])([F:26])[F:27])=[CH:23][CH:22]=[CH:21][N:20]=1

Participants

5

Reactant 1

HCID 59352270HCID 59352270, compound

Product 1

HCID 59352354HCID 59352354, compoundYield 33.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalyst2×HCID 9942167Palladium hydroxideCatalyst2×HCID 887MethanolSolvent

Procedure

A mixture of 4′-(benzylamino)-1′-{[3-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.251 g, 0.45 mmol) and palladium hydroxide on carbon (0.251 g, 20 dry wt %, contains −50% water, 0.18 mmol), methanol (20 mL), glacial acetic acid (1 drop, catalytic amount) was placed under an atmosphere of hydrogen (1 atm) and stirred at ambient temperature for 16 h. Further, palladium hydroxide on carbon (0.100 g, 20 dry wt %, contains −50% water, 0.072 mmol) and acetic acid (1 drop, catalytic amount) were added, the reaction mixture was again placed under an atmosphere of hydrogen (1 atm) and allowed to react at ambient temperature for 72 h. The reaction mixture was filtered through a pad of diatomaceous earth and the pad was washed with ethyl acetate (50 mL). The filtrate was washed with water (100 mL) and brine (100 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with a 0% to 25% gradient of ethyl acetate in dichloromethane, to yield 4′-amino-1′-{[3-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.070 g, 33%) as a colorless solid: mp 243-245° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.68 (d, J=4.6 Hz, 1H), 8.25 (d, J=7.9 Hz, 1H), 7.58 (dd, J=7.7 Hz, J=5.0 Hz, 1H), 6.91 (dd, J=8.0 Hz, J=8.0 Hz, 1H), 6.54 (d, J=12.1 Hz, 1H), 6.33 (d, J=8.2 Hz, 1H), 6.08 (d, J=7.6 Hz, 1H), 5.14 (ABq, 2H), 4.71 (ABq, 2H), 4.52 (s, 2H), 4.17 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 178.0, 154.9, 152.6, 152.4, 144.7, 142.9, 142.8, 138.8, 134.2, 134.1, 129.4, 122.0, 118.6, 114.5, 112.8, 111.3, 99.0, 77.2, 64.5, 63.9, 57.2, 42.4; MS (ES+) m/z 469.9 (M+1).

Workup

  1. customto react at ambient temperature for 72 h
  2. filtrationThe reaction mixture was filtered through a pad of diatomaceous earth
  3. washthe pad was washed with ethyl acetate (50 mL)
  4. washThe filtrate was washed with water (100 mL) and brine (100 mL)
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography
  9. washeluted with a 0% to 25% gradient of ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-a80508c07d9b4b1485ee0c94bdac85a0
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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