Hydrochloric Acid → HCID 67315615, compound

HRID 1254112Notes

Reaction equation

HRID 1254112 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][CH:23]1[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][CH2:31][C:32]2[N:37]=[C:36]3[CH2:38][O:39][C:40](=O)[C:35]3=[CH:34][CH:33]=2)[CH2:25][CH2:24]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:40]1[C:35]2[C:36](=[N:37][C:32]([CH2:31][CH2:30][CH2:29][N:26]3[CH2:27][CH2:28][CH:23]([OH:22])[CH2:24][CH2:25]3)=[CH:33][CH:34]=2)[CH2:38][O:39]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 58478796HCID 58478796, compound

Product 1

HCID 67315615HCID 67315615, compoundYield 3.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 5-fluoro-1,3-dihydro-indol-2-one (163 mg, 1.09 mmol.) in THF (2 mL) is placed under an argon atmosphere cooled in an ice bath. A solution of lithium bis(trimethylsilyl)amide (3.6 mL of a 1M in THF, 3.6 mmol, 5 eq.) is added slowly at 0° C. and the resulting solution is stirred for 20 min. The ice-bath is then removed and a solution of 2-[3-(4-Hydroxy-piperidin-1-yl)-propyl]-7H-furo[3,4-b]pyridin-5-one (200 mg, 0.72 mmol) in THF (1 mL) is added dropwise to the reaction mixture. The lactone does not dissolve well, so rest of the lactone is added as a solid. The resulting solution is stirred for 3 h and then poured into 10% aqueous HCl solution (50 mL) and stirred for 48 h at room temperature. Extraction with EtOAc followed by chromatography (silica gel, MeOH/Chloroform) provides the title compound (10 mg) as a solid.

Workup

  1. temperaturecooled in an ice bath
  2. customThe ice-bath is then removed
  3. additionis added as a solid
  4. stirringThe resulting solution is stirred for 3 h
  5. stirringstirred for 48 h at room temperature
  6. extractionExtraction with EtOAc

Sources & evidence

ORD record
ord-f7e6b3c4b8e643e7860cf755507108a8
Source dataset
uspto-grants-2013_06
Patent number
US08455535B2

Reaction notes

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