Sodium hydride → 1,3-dihydro-3,3-bis(2-fluoro-4-pyridinylmethyl)-1-(4-morpholinyl)-2H-indol-2-one

HRID 22233Notes

Reaction equation

HRID 22233 reaction equation
[H-].[Na+].[N:3]1([N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][C:10]2=[O:18])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[F:19][C:20]1[CH:25]=[C:24]([CH2:26]Cl)[CH:23]=[CH:22][N:21]=1>O1CCCC1>[F:19][C:20]1[CH:25]=[C:24]([CH2:26][C:11]2([CH2:26][C:24]3[CH:23]=[CH:22][N:21]=[C:20]([F:19])[CH:25]=3)[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:9]([N:3]3[CH2:4][CH2:5][O:6][CH2:7][CH2:8]3)[C:10]2=[O:18])[CH:23]=[CH:22][N:21]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 108445134-(Chloromethyl)-2-fluoropyridineHCID 152843961,3-dihydro-1-(4-morpholinyl)-2H-indol-2-one

Product 1

HCID 99546911,3-dihydro-3,3-bis(2-fluoro-4-pyridinylmethyl)-1-(4-morpholinyl)-2H-indol-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% oil dispension 92 mg, 2.3 mmole) was charged to a flame-dried flask and washed with pentane (3×3 ml). The flask was flushed with nitrogen, tetrahydrofuran (10 ml) was added and the slurry was stirred at 0° C. 1,3-dihydro-1-(4-morpholinyl)-2H-indol-2-one (225 mg, 1.0 mole) was added, the resulting solution was stirred for 15 minutes at room temperature and recooled to 0° C. A solution of 2-Fluoro-4-picolyl chloride (410 mg, 2.3 mmole) in tetrahydrofuran (10 ml) was added and the solution allowed to stir at room temperature overnight. The reaction was quenched into water (40 ml) and extracted with dichloromethane(3×25 ml). The combined organics were washed with brine, dried over magnesium sulfate, filter and concentrated under reduced pressure. The residue was chromatographed on silica gel or directly recrystallized from chloroform/hexane to give the desired product; m.p. 198°-203° C. Anal. (C24H22F2N4O2 ·0.25H2O): C,H,N,F.

Workup

  1. washwashed with pentane (3×3 ml)
  2. customThe flask was flushed with nitrogen, tetrahydrofuran (10 ml)
  3. additionwas added
  4. stirringthe resulting solution was stirred for 15 minutes at room temperature
  5. customrecooled to 0° C
  6. stirringto stir at room temperature overnight
  7. customThe reaction was quenched into water (40 ml)
  8. extractionextracted with dichloromethane(3×25 ml)
  9. washThe combined organics were washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfilter
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was chromatographed on silica gel
  14. customdirectly recrystallized from chloroform/hexane

Sources & evidence

ORD record
ord-a6919f060546461c9b74ef1274449872
Source dataset
uspto-grants-1995_06
Patent number
US05428035

Reaction notes

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