Hydrochloric Acid → HCID 67314442, compound

HRID 1254113Notes

Reaction equation

HRID 1254113 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]([CH2:38][CH3:39])[CH2:25][CH2:26][CH2:27][C:28]1[N:33]=[C:32]2[CH2:34][O:35][C:36](=O)[C:31]2=[CH:30][CH:29]=1)[CH3:23].C1(C2C(=CC=CC=2)CO1)=O.Cl.C([O-])(O)=O.[Na+]>C1COCC1>[CH2:38]([N:24]([CH2:22][CH3:23])[CH2:25][CH2:26][CH2:27][C:28]1[N:33]=[C:32]2[CH2:34][O:35][C:36](=[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:31]2=[CH:30][CH:29]=1)[CH3:39]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 6885PhthalideHCID 516892Sodium BicarbonateHCID 2733832Lithium HexamethyldisilazideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 58478813HCID 58478813, compound

Product 1

HCID 67314442HCID 67314442, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-Fluoro-1,3-dihydro-indol-2-one (100 mg) in anhydrous. THF (5 mL) at room temperature is treated with lithium bis(trimethylsilyl)amide (1.0 M solution in tetrahydrofuran, 1.33 mL, 6 equiv). The resulting mixture is stirred at room temperature for 10 min, then is added 2-(3-diethylamino-propyl)-7H-furo[3,4-b]pyridin-5-one (55 mg, 1 equiv) in one portion. The reaction mixture is stirred at room temperature until both TLC and HPLC indicated the disappearance of the phthalide. The reaction mixture is poured into 10% aqueous HCl solution (10 mL) with stirring. Then it is heated at 50° C. for 2 h and further stirred at room temperature for an overnight. The mixture is poured into 100 mL ice water, to which solid NaHCO3 is carefully added to adjust pH to 8. The aqueous layer is extracted with EtOAc (2×). Organic layer is combined, dried with anhydrous Na2SO4, filtered and concentrated. The residue obtained purified by chromatography (silica gel, MeOH-chloroform) to give the title compound as a yellow solid (31 mg, 37%).

Workup

  1. stirringThe reaction mixture is stirred at room temperature until both TLC and HPLC
  2. stirringwith stirring
  3. temperatureThen it is heated at 50° C. for 2 h
  4. stirringfurther stirred at room temperature for an overnight
  5. additionis carefully added
  6. extractionThe aqueous layer is extracted with EtOAc (2×)
  7. dry with materialdried with anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue obtained
  11. custompurified by chromatography (silica gel, MeOH-chloroform)

Sources & evidence

ORD record
ord-956846dd92bd40b1a9be630b0c09a33a
Source dataset
uspto-grants-2013_06
Patent number
US08455535B2

Reaction notes

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