Propargyl alcohol → N-[(4-chlorophenyl)methyl]-7-ethyl-2-(3-hydroxyprop-1-ynyl)-4-oxo-thieno[2,3-b]pyridine-5-carboxamide

HRID 1978939Notes

Reaction equation

HRID 1978939 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:22])[C:12]3[CH:20]=[C:19](I)[S:18][C:13]=3[N:14]([CH2:16][CH3:17])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.[CH2:25]([OH:28])[C:26]#[CH:27]>C(NCC)C.[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:22])[C:12]3[CH:20]=[C:19]([C:27]#[C:26][CH2:25][OH:28])[S:18][C:13]=3[N:14]([CH2:16][CH3:17])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 7859Propargyl alcoholHCID 9847660HCID 9847660, compound

Product 1

HCID 6483693N-[(4-chlorophenyl)methyl]-7-ethyl-2-(3-hydroxyprop-1-ynyl)-4-oxo-thieno[2,3-b]pyridine-5-carboxamideYield 70%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8021DiethylamineSolvent

Procedure

To a suspension of N-(4-chlorobenzyl)-7-ethyl-2-iodo-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide (Example No. 12) (0.267 g) in diethylamine (14 mL) is added copper iodide (0.032 g) and Pd(PPh3)2Cl2 (0.009 g) followed by addition of propargyl alcohol (39 μL). The reaction is stirred at rt for 18 h. The diethylamine is removed in vacuo, and the resulting residue is partitioned between H2O (25 mL) and CH2Cl2 (25 mL). The organic layer is removed, and the aqueous layer is extracted with CH2Cl2 (3×25 mL). The combined organic layers are dried with MgSO4, filtered, and concentrated in vacuo. The resulting orange solid is purified by column chromatography (CH2Cl2:CH3OH, 98:2). Fractions homogeneous by TLC are combined and concentrated in vacuo to yield 0.158 g (70%) of the title compound as a yellow, crystalline solid.

Workup

  1. customThe diethylamine is removed in vacuo
  2. customthe resulting residue is partitioned between H2O (25 mL) and CH2Cl2 (25 mL)
  3. customThe organic layer is removed
  4. extractionthe aqueous layer is extracted with CH2Cl2 (3×25 mL)
  5. dry with materialThe combined organic layers are dried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting orange solid is purified by column chromatography (CH2Cl2:CH3OH, 98:2)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-316a12e31b374a0ab4a81df9e650bec2
Source dataset
uspto-grants-2001_05
Patent number
US06239142B1

Reaction notes

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