Tetrahydrofuran → (3E)-6-fluoro-3-{4-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl]methyl)phenyl}-5,5-dimethylfuran-2(5H)-ylidene}-1,3-dihydro-2H-indol-2-one

HRID 537922Notes

Reaction equation

HRID 537922 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5](/[C:6](=[C:12]3/[CH:13]=[C:14]([C:19]4[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=4)[C:15]([CH3:18])([CH3:17])[O:16]/3)/[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[N:27]1([CH2:33][CH2:34][O:35][CH2:36][CH2:37][OH:38])[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C([BH3-])#N.[Na+].C1COCC1.C([O-])(O)=O.[Na+]>CN(C=O)C.CO.O.CC(O)=O>[F:1][C:2]1[CH:10]=[C:9]2[C:5](/[C:6](=[C:12]3\[O:16][C:15]([CH3:18])([CH3:17])[C:14]([C:19]4[CH:20]=[CH:21][C:22]([CH2:23][N:30]5[CH2:31][CH2:32][N:27]([CH2:33][CH2:34][O:35][CH2:36][CH2:37][OH:38])[CH2:28][CH2:29]5)=[CH:25][CH:26]=4)=[CH:13]\3)/[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1

Participants

10

Reactant 5

HCID 8028TetrahydrofuranHCID 1394361-[2-(2-Hydroxyethoxy)ethyl]piperazineHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 589264404-[(5E)-5-(6-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]benzaldehyde

Product 1

HCID 58926034(3E)-6-fluoro-3-{4-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl]methyl)phenyl}-5,5-dimethylfuran-2(5H)-ylidene}-1,3-dihydro-2H-indol-2-one

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-[(5E)-5-(6-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]benzaldehyde (55 mg, 0.16 mmol), 2-(2-(piperazin-1-yl)ethoxy)ethanol (56 mg, 0.32 mmol) and 4 Å molecular sieves (100 mg) in anhydrous DMF (3 mL) was stirred at room temp for 16 hours. To this stirred mixture was added AcOH (10 mg), 1M sodium cyanoborohydride in THF solution (0.32 mL, 0.32 mmol) and 3 mL of anhydrous methanol. The reaction mixture was stirred at room temp for 5 hours and poured into 100 mL of water. Saturated NaHCO3 solution was then added until pH=9. The precipitates were filtered, washed with water, and dried in vacuo to give the crude product, which was purified through silica gel column with 5-10% MeOH/CHCl3 to give (3E)-6-fluoro-3-{4-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl]methyl)phenyl}-5,5-dimethylfuran-2(5H)-ylidene}-1,3-dihydro-2H-indol-2-one as yellow solid. Yield: 45 mg, 56%.

Workup

  1. stirringThe reaction mixture was stirred at room temp for 5 hours
  2. filtrationThe precipitates were filtered
  3. washwashed with water
  4. customdried in vacuo
  5. customto give the crude product, which
  6. customwas purified through silica gel column with 5-10% MeOH/CHCl3

Sources & evidence

ORD record
ord-23f04b7bdbe443c0ad8e6ba4d2feaec3
Source dataset
uspto-grants-2014_10
Patent number
US08865682B2

Reaction notes

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