Sodium Carbonate → 4'-pyrimidin-5-yl-1'-{[5-(trifluoromethyl)-2-furyl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1'H)-one

HRID 425653Notes

Reaction equation

HRID 425653 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([CH2:25][O:24][C:23]3[CH:26]=[C:27]4[C:31](=[CH:32][C:22]1=3)[CH2:30][CH2:29][O:28]4)[C:5](=[O:21])[N:6]2[CH2:11][C:12]1[O:13][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:16]=1.[N:33]1[CH:38]=[C:37](B(O)O)[CH:36]=[N:35][CH:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[N:33]1[CH:38]=[C:37]([C:2]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:3]=2[C:4]2([CH2:25][O:24][C:23]4[CH:26]=[C:27]5[C:31](=[CH:32][C:22]2=4)[CH2:30][CH2:29][O:28]5)[C:5](=[O:21])[N:6]3[CH2:11][C:12]2[O:13][C:14]([C:17]([F:18])([F:20])[F:19])=[CH:15][CH:16]=2)[CH:36]=[N:35][CH:34]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 592634504'-bromo-1'-((5-(trifluoromethyl)furan-2-yl)methyl)-5,6-dihydro-2H-spiro[benzofuro[6,5-b]furan-3,3'-indolin]-2'-one

Product 1

HCID 592634724'-pyrimidin-5-yl-1'-{[5-(trifluoromethyl)-2-furyl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1'H)-oneYield 28.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 4′-bromo-1′-{[5-(trifluoromethyl)-2-furyl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.11 g, 0.21 mmol), pyrimidine-5-boronic acid (0.04 g, 0.33 mmol), tetrakis(triphenylphosphine)palladium(0) (0.03 g, 0.02 mmol), 2.00 M sodium carbonate (1.00 mL) and 1,2-dimethoxyethane (10.0 mL) was heated at reflux for 16 h under nitrogen. After the organic solvent was evaporated in vacuo, the black residue was extracted with ethyl acetate (3×35.0 mL). The combined organic layers was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography eluting with ethyl acetate:hexane (35%) to afford the title compound (0.03 g, 26%): mp 263-266° C.; 1H NMR (300 MHz, CDCl3) δ 9.10 (s, 1H), 8.14 (s, 2H), 7.39 (t, 1H), 7.10, (d, 1H), 6.87 (d, 1H), 6.76 (s, 1H), 6.51 (s, 1H), 6.46 (s, 1H), 6.07 (s, 1H), 5.03 (ABq, 2H), 4.62-4.48 (m, 2H), 4.58 (ABq, 2H), 3.01 (t, 2H); 13C NMR (75 MHz, CDCl3) δ 177.3, 162.5, 161.0, 157.4, 155.9, 151.6, 142.2, 141.7, 132.8, 132.3, 131.3, 129.3, 125.7, 120.6, 120.2, 118.3, 117.0, 112.7, 109.7, 109.4, 93.5, 78.9, 72.5, 57.7, 37.1, 28.9; MS (ES+) m/z 506.5 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 16 h under nitrogen
  3. customAfter the organic solvent was evaporated in vacuo
  4. extractionthe black residue was extracted with ethyl acetate (3×35.0 mL)
  5. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-0d75aaa3115048f9a1a11b4c4ab7b590
Source dataset
uspto-grants-2012_01
Patent number
US08106087B2

Reaction notes

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