Benzylamine → HCID 59352270, compound

HRID 2385528Notes

Reaction equation

HRID 2385528 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:34]3[C:25](=[CH:26][C:27]4[O:32][CH2:31][CH2:30][O:29][C:28]=4[CH:33]=3)[O:24][CH2:23]1)[C:5](=[O:22])[N:6]2[CH2:11][C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:15]=[CH:14][N:13]=1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:87]([NH2:94])[C:88]1[CH:93]=[CH:92][CH:91]=[CH:90][CH:89]=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:87]([NH:94][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:34]3[C:25](=[CH:26][C:27]4[O:32][CH2:31][CH2:30][O:29][C:28]=4[CH:33]=3)[O:24][CH2:23]1)[C:5](=[O:22])[N:6]2[CH2:11][C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:15]=[CH:14][N:13]=1)[C:88]1[CH:93]=[CH:92][CH:91]=[CH:90][CH:89]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 68597194HCID 68597194, compound

Product 1

HCID 59352270HCID 59352270, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

4′-Bromo-1′-{[3-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.700 g, 1.31 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.14 g, 0.16 mmol), sodium tert-butoxide (0.252 g, 2.62 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (0.29 g, 0.47 mmol) and benzylamine (0.22 mL, 2.0 mmol) were combined in anhydrous toluene (20 mL) and heated at 105° C. for 60 h. The reaction mixture was filtered through a pad of diatomaceous earth and the pad was washed with ethyl acetate (150 mL). The filtrate was washed with saturated aqueous sodium bicarbonate (100 mL), water (100 mL) and brine (100 mL), dried over anhydrous 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 afford 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 (0.227 g, 31%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.67 (d, J=4.5 Hz, 1H), 7.95 (d, J=7.9 Hz, 1H), 7.34-7.17 (m, 5H), 7.02 (d, J=7.7 Hz, 1H), 6.95 (dd, J=8.3, 8.3 Hz, 1H), 6.83 (s, 1H), 6.40 (s, 1H), 6.15 (ABq, 2H), 5.23 (ABq, 2H), 4.86 (ABq, 2H), 4.20-4.15 (m, 4H).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of diatomaceous earth
  2. washthe pad was washed with ethyl acetate (150 mL)
  3. washThe filtrate was washed with saturated aqueous sodium bicarbonate (100 mL), water (100 mL) and brine (100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluted with a 0% to 25% gradient of ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-2890fcf9087248b9b34f933fbce0d28a
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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