Water → 1'-[(2-methoxypyrimidin-5-yl)methyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1'H)-one

HRID 1407714Notes

Reaction equation

HRID 1407714 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:13][O:12][C:11]3[CH:14]=[C:15]4[C:19](=[CH:20][C:10]2=3)[CH2:18][CH2:17][O:16]4)[C:2]1=[O:21].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:29][C:30]1[CH:31]=[N:32][C:33]([O:36][CH3:37])=[N:34][CH:35]=1.O>CN(C)C=O>[CH3:37][O:36][C:33]1[N:34]=[CH:35][C:30]([CH2:29][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]3([CH2:13][O:12][C:11]4[CH:14]=[C:15]5[C:19](=[CH:20][C:10]3=4)[CH2:18][CH2:17][O:16]5)[C:2]2=[O:21])=[CH:31][N:32]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonate2×HCID 216981735-(Chloromethyl)-2-methoxypyrimidine2×HCID 592633545,6-dihydro-2H-spiro[benzofuro[6,5-b]furan-3,3'-indolin]-2'-one

Product 1

HCID 593521211'-[(2-methoxypyrimidin-5-yl)methyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1'H)-oneYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.28 g, 1.0 mmol) in dry N,N-dimethylformamide (6 mL) was added cesium carbonate (2.30 g, 7.1 mmol) at ambient temperature. The mixture was stirred at ambient temperature for 30 min, and 5-(chloromethyl)-2-methoxypyrimidine (0.34 g, 2.1 mmol) in dry N,N-dimethylformamide (3 mL) was added dropwise. The mixture was stirred at ambient temperature for 16 h, and additional cesium carbonate (0.68 g, 2.1 mmol) and 5-(chloromethyl)-2-methoxypyrimidine (0.20 g, 1.3 mmol) were added. The mixture was stirred at ambient temperature for 64 h. Water (60 mL) was added and the mixture was extracted with ethyl acetate (3×60 mL). The combined organic solution was washed with brine (100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate 1:1) to afford 1′-[(2-methoxypyrimidin-5-yl)methyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.29 g, 73%) as a colorless solid: mp 203-204° C.; 1H NMR (300 MHz, CDCl3) δ8.57 (s, 2H), 7.30-7.23 (m, 1H), 7.22-7.17 (m, 1H), 7.11-7.04 (m, 1H), 6.86-6.81 (m, 1H), 6.44-6.41 (m, 2H), 4.89 (ABq, 2H), 4.81 (ABq, 2H), 4.59-4.50 (m, 2H), 4.01 (s, 3H), 3.10-2.90 (m, 2H); 13C NMR (75 MHz, CDCl3) δ177.9, 165.4, 161.9, 161.3, 158.8, 141.1, 132.7, 128.8, 124.3, 123.9, 122.8, 120.1, 119.7, 118.7, 108.5, 93.3, 80.5, 72.4, 57.6, 55.1, 38.8, 29.0; MS (ES+) m/z 402.1 (M+1).

Workup

  1. stirringThe mixture was stirred at ambient temperature for 16 h
  2. stirringThe mixture was stirred at ambient temperature for 64 h
  3. extractionthe mixture was extracted with ethyl acetate (3×60 mL)
  4. washThe combined organic solution was washed with brine (100 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (hexanes/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-4382b6fd01c4476e8cc99e2d92c25fc5
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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