Diisopropylamine → N-(4-Chlorobenzyl)-2-formyl-3-[(2-methoxyethoxy)methyl]-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide

HRID 23635Notes

Reaction equation

HRID 23635 reaction equation
[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:26])[C:12]3[S:19][CH:18]=[C:17]([CH2:20][O:21][CH2:22][CH2:23][O:24][CH3:25])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.C(NC(C)C)(C)C.C([Li])CCC.C1C[O:52][CH2:51]C1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:26])[C:12]3[S:19][C:18]([CH:51]=[O:52])=[C:17]([CH2:20][O:21][CH2:22][CH2:23][O:24][CH3:25])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:27][CH:28]=1

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 8028Tetrahydrofuran3×HCID 2724682Lithium diisopropylamideHCID 22574322N-(4-chlorobenzyl)-3-[(2-methoxyethoxy)methyl]-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamideHCID 178418339Butyllithium

Product 1

HCID 22574380N-(4-Chlorobenzyl)-2-formyl-3-[(2-methoxyethoxy)methyl]-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-78 °C

Procedure

A mixture of 210 mg of N-(4-chlorobenzyl)-3-[(2-methoxyethoxy)methyl]-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide and 5.0 mL of dry THF is heated to boiling under argon to dissolve the solid, then is cooled to −78° C. Into this mixture is cannulated a solution of LDA in THF, prepared in the usual manner from 0.35 mL of diisopropylamine and 0.80 mL of 2.5 M (in hexane) butyllithium in 4.0 mL of THF. The resulting deep blue mixture is stirred at −78° C. for 15 min, then 0.25 mL of dry DMF is added and the mixture allowed to warm to ambient temperature. The mixture is then partitioned between CH2Cl2 and dil HCl, and the organic phase dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography on silica gel using 2% MeOH in CH2Cl2 provides 146 mg of the title compound as an orange solid. Recrystallization of a sample from EtOAc provides an analytical sample as a white solid.

Workup

  1. temperatureis heated
  2. dissolutionto dissolve the solid
  3. temperatureto warm to ambient temperature
  4. customThe mixture is then partitioned between CH2Cl2 and dil HCl
  5. dry with materialthe organic phase dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5798a8d469524759a87eddbf99f440cc
Source dataset
uspto-grants-2005_02
Patent number
US06852731B2

Reaction notes

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