Hydrochloric Acid → HCID 67314433, compound

HRID 1011373Notes

Reaction equation

HRID 1011373 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+].[OH:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][CH2:36][C:37]2[N:42]=[C:41]3[CH2:43][O:44][C:45](=O)[C:40]3=[CH:39][CH:38]=2)[CH2:30][CH2:29]1.Cl.C([O-])(O)=O.[Na+]>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:45]1[C:40]2[C:41](=[N:42][C:37]([CH2:36][CH2:35][CH2:34][N:31]3[CH2:30][CH2:29][N:28]([CH2:27][CH2:26][O:25][CH2:24][CH2:23][OH:22])[CH2:33][CH2:32]3)=[CH:38][CH:39]=2)[CH2:43][O:44]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 2733832Lithium HexamethyldisilazideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 58478812HCID 58478812, compound

Product 1

HCID 67314433HCID 67314433, compoundYield 34.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 5-fluoro-1,3-dihydro-indol-2-one (143 mg, 0.95 mmol) in THF (4 mL) at room temperature is treated with lithium bis(trimethylsilyl)amide (1.0 M solution in tetrahydrofuran, 2.2 mL, 2.2 mmol) and stirred for 10 min. A solution of 2-(3-{4-[2-(2-Hydroxy-ethoxy)-ethyl]-piperazin-1-yl}-propyl)-7H-furo[3,4-b]pyridin-5-one (110 mg, 0.31 mmol) in anhydrous THF (2 mL) is added. The reaction mixture is stirred at room temperature for 2 h. The reaction mixture is poured into aqueous 2N HCl (10 mL) with stirring and is heated at 60° C. for 2.5 h. The mixture is then poured into 100 mL ice water, to which solid NaHCO3 is carefully added to adjust pH to 8. The aqueous layer is extracted with chloroform (3×). The combined organic layers are dried with anhydrous Na2SO4, and concentrated. The residue purified by column chromatography (MeOH-chloroform) to give the title compound as a yellow solid (51 mg, 34%).

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 2 h
  2. stirringwith stirring
  3. additionis carefully added
  4. extractionThe aqueous layer is extracted with chloroform (3×)
  5. dry with materialThe combined organic layers are dried with anhydrous Na2SO4
  6. concentrationconcentrated
  7. customThe residue purified by column chromatography (MeOH-chloroform)

Sources & evidence

ORD record
ord-582dfec7675f4c4dad43c50a5b15bf5c
Source dataset
uspto-grants-2011_07
Patent number
US07977351B2

Reaction notes

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