Hydrochloric Acid → HCID 67314628, compound

HRID 1254090Notes

Reaction equation

HRID 1254090 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:22]([N:24]([CH2:40][CH3:41])[CH2:25][CH2:26][N:27]([CH2:29][C:30]1[N:35]=[C:34]2[CH2:36][O:37][C:38](=O)[C:33]2=[CH:32][CH:31]=1)[CH3:28])[CH3:23].Cl>C1COCC1>[CH2:40]([N:24]([CH2:22][CH3:23])[CH2:25][CH2:26][N:27]([CH2:29][C:30]1[N:35]=[C:34]2[CH2:36][O:37][C:38](=[C:5]3[C:4]4[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=4)[NH:7][C:6]3=[O:11])[C:33]2=[CH:32][CH:31]=1)[CH3:28])[CH3:41]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 59665587HCID 59665587, compound

Product 1

HCID 67314628HCID 67314628, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 5-fluoro-1,3-dihydro-indol-2-one (125 mg, 0.83 mmol.) in THF (4 mL) is treated with a solution of lithium bis(trimethylsilyl)amide (1.66 mL of a 1M solution in THF, 1.66 mmol) dropwise. The resulting solution is stirred for 20 min at room temperature. A solution of 2-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-7H-furo[3,4-b]pyridin-5-one (115 mg, 0.41 mmol) in THF (1.5 mL) is added dropwise to the reaction mixture. The resulting solution is stirred at room temperature for 4 h and then poured into 10% aqueous HCl solution (30 mL) previously cooled to 0° C. The ice bath is removed and the solution is stirred at room temperature for 16 h. The yellow solution is then cooled and solid NaHCO3 is carefully added to adjust the solution to pH=8. The aqueous layer is extracted with EtOAc. The combined organic extracts are dried with anhydrous Na2SO4 and concentrated. The solid residue is broken up in isopropyl alcohol to give a yellow solid. The yellow solid is collected by filtration to give the title compound (102 mg, 61%).

Workup

  1. stirringThe resulting solution is stirred at room temperature for 4 h
  2. temperaturepreviously cooled to 0° C
  3. customThe ice bath is removed
  4. stirringthe solution is stirred at room temperature for 16 h
  5. temperatureThe yellow solution is then cooled
  6. additionsolid NaHCO3 is carefully added
  7. extractionThe aqueous layer is extracted with EtOAc
  8. dry with materialThe combined organic extracts are dried with anhydrous Na2SO4
  9. concentrationconcentrated
  10. customto give a yellow solid
  11. filtrationThe yellow solid is collected by filtration

Sources & evidence

ORD record
ord-cb62403412ab42f8b8768c3989fab0d4
Source dataset
uspto-grants-2013_06
Patent number
US08455535B2

Reaction notes

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