Sodium Carbonate → 4'-[6-(dimethylamino)pyridin-3-yl]-1'-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1H)-one

HRID 1965771Notes

Reaction equation

HRID 1965771 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([CH2:21][O:20][C:19]3[CH:22]=[C:23]4[C:27](=[CH:28][C:18]1=3)[CH2:26][CH2:25][O:24]4)[C:5](=[O:17])[N:6]2[CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][O:13]1.O.[CH3:30][N:31]([CH3:41])[C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][N:33]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.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>[CH3:30][N:31]([CH3:41])[C:32]1[N:33]=[CH:34][C:35]([C:2]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:3]=2[C:4]2([CH2:21][O:20][C:19]4[CH:22]=[C:23]5[C:27](=[CH:28][C:18]2=4)[CH2:26][CH2:25][O:24]5)[C:5](=[O:17])[N:6]3[CH2:11][C@H:12]2[CH2:16][CH2:15][CH2:14][O:13]2)=[CH:36][CH:37]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 441190932-(Dimethylamino)pyridine-5-boronic acid hydrateHCID 593527104'-bromo-1'-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1'H)-one

Product 1

HCID 593526424'-[6-(dimethylamino)pyridin-3-yl]-1'-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1H)-oneYield 75.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A stirred solution of 4′-bromo-1′-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.125 g, 0.3 mmol), 2-(dimethylamino)pyridine 5-boronic acid hydrate (0.08 g, 0.45 mmol), tetrakis(triphenylphosphine)palladium(0) (0.04 g, 0.03 mmol), 2 M sodium carbonate (1 mL) in N,N-dimethylformamide (4 mL) was heated with stirring at 150° C. for 15 min in a microwave reactor. The solution was poured into distilled water (15 mL) and washed with ethyl acetate (75 mL). The ethyl acetate layer was washed with brine (3×25 mL), dried on magnesium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by flash chromatography with ethyl acetate in hexanes (gradient: 30% to 60%) to afford 4′-[6-(dimethylamino)pyridin-3-yl]-1′-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1H)-one (0.11 g, 73%) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) δ7.53 (d, J=2.4 Hz, 1H), 7.33 (dd, J=7.8 Hz, 1H), 7.18 (dd, J=7.4, 4.7 Hz, 1H), 6.77 (d, J=7.2 Hz, 1H), 6.71 (ddd, J=8.8, 2.4, 0.9 Hz, 1H), 6.51 (d, J=5.6 Hz, 1H), 6.31 (d, J=8.8 Hz, 1H), 6.12 (d, J=0.9 Hz, 1H), 4.59-4.41 (m, 3H), 4.33 (dd, J=9.4, 3.1 Hz, 1H), 4.23-4.08 (m, 1H), 3.89-3.55 (m, 4H), 3.09-2.86 (m, 2H), 2.95 (s, 6H), 2.05-1.69 (m, 3H), 1.67-1.51 (m, 1H); MS (ES+) m/z 484.1 (M+1).

Workup

  1. additionThe solution was poured
  2. distillationinto distilled water (15 mL)
  3. washwashed with ethyl acetate (75 mL)
  4. washThe ethyl acetate layer was washed with brine (3×25 mL)
  5. customdried on magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to dryness
  8. customThe residue was purified by flash chromatography with ethyl acetate in hexanes (gradient: 30% to 60%)

Sources & evidence

ORD record
ord-55f7fad7f3164eaba37fcb504d9e4e79
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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