Hydrochloric Acid → HCID 67314542, compound

HRID 1254085Notes

Reaction equation

HRID 1254085 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+].[N:22]1([CH2:28][C:29]2[N:34]=[C:33]3[CH2:35][O:36][C:37](=O)[C:32]3=[CH:31][CH:30]=2)[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.Cl>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[C:37]1[C:32]2[C:33](=[N:34][C:29]([CH2:28][N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:30][CH:31]=2)[CH2:35][O:36]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 67315653HCID 67315653, compound

Product 1

HCID 67314542HCID 67314542, compoundYield 35.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 5-fluoro-1,3-dihydro-indol-2-one (113 mg, 0.75 mmol.) in THF (1 mL) is placed under an argon atmosphere cooled in an ice bath. A solution of lithium bis(trimethylsilyl)amide (2 mL of a 1M solution in THF, 2 mmol) is added slowly at 0° C. and the resulting solution is stirred for 10 min. The ice-bath is removed and a solution of 2-morpholin-4-ylmethyl-7H-furo[3,4-b]pyridin-5-one (120 mg, 0.5 mmol) in THF (2 mL) is added dropwise to the reaction mixture. The resulting solution is stirred for 4 h and then poured into a 10% aqueous HCl solution. The resulting solution is stirred for 48 h at room temperature. The solid which precipitated from solution is collected by filtration and washed sequentially with small volumes of MeOH, EtOAc, Et2O (3×5 mL). The residual solid is purified by chromatography (silica gel, 5% MeOH in EtOAc). The product containing fractions are concentrated to give the title compound as a yellow solid (65 mg, 35%).

Workup

  1. temperaturecooled in an ice bath
  2. customThe ice-bath is removed
  3. stirringThe resulting solution is stirred for 4 h
  4. stirringThe resulting solution is stirred for 48 h at room temperature
  5. customThe solid which precipitated from solution
  6. filtrationis collected by filtration
  7. washwashed sequentially with small volumes of MeOH, EtOAc, Et2O (3×5 mL)
  8. customThe residual solid is purified by chromatography (silica gel, 5% MeOH in EtOAc)
  9. additionThe product containing fractions
  10. concentrationare concentrated

Sources & evidence

ORD record
ord-c2571aa6fe014126bbb416fda6776832
Source dataset
uspto-grants-2013_06
Patent number
US08455535B2

Reaction notes

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