Propargyl alcohol → HCID 178522937, compound

HRID 2299288Notes

Reaction equation

HRID 2299288 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11]([OH:20])=[C:12]3[CH:18]=[C:17](I)[S:16][C:13]3=[N:14][CH:15]=2)=[O:9])=[CH:4][CH:3]=1.[CH2:23]([OH:26])[C:24]#[CH:25]>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:22]=[CH:21][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11]([OH:20])=[C:12]3[CH:18]=[C:17]([C:25]#[C:24][CH2:23][OH:26])[S:16][C:13]3=[N:14][CH:15]=2)=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 7859Propargyl alcoholHCID 178522942HCID 178522942, compound

Product 1

HCID 178522937HCID 178522937, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8021DiethylamineSolvent

Procedure

To a suspension of N-(4-chlorobenzyl)-4-hydroxy-2-iodothieno[2,3-b]pyridine-5-carboxamide (Example No. 2) (1.00 g) in diethylamine (28 mL) is added copper iodide (0.128 g) and Pd(PPh3)2Cl2 (0.032 g) followed by addition of propargyl alcohol (0.16 mL). The reaction is stirred at rt for 3 d. The reaction mixture is partitioned between H2O (100 mL) and ethyl acetate (100 mL). The organic layer is removed, and the aqueous layer is extracted with ethyl acetate (2×100 mL). Combined organic layers are washed with a saturated aqueous NH4Cl solution, dried with MgSO4, filtered, and concentrated in vacuo. The resulting orange solid is purified via column chromatography (CH2Cl2:CH3OH; 98:2, 95:5). Fractions homogeneous by TLC are combined and concentrated in vacuo to yield a pale orange solid which is recrystallized from CH2Cl2/CH3OH to yield 0.165 g (20%) of the title compound as an off-white solid.

Workup

  1. customThe reaction mixture is partitioned between H2O (100 mL) and ethyl acetate (100 mL)
  2. customThe organic layer is removed
  3. extractionthe aqueous layer is extracted with ethyl acetate (2×100 mL)
  4. washCombined organic layers are washed with a saturated aqueous NH4Cl solution
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting orange solid is purified via column chromatography (CH2Cl2:CH3OH; 98:2, 95:5)
  9. concentrationconcentrated in vacuo
  10. customto yield a pale orange solid which
  11. customis recrystallized from CH2Cl2/CH3OH

Sources & evidence

ORD record
ord-84502238766a4efa9a41017698172c7b
Source dataset
uspto-grants-2002_12
Patent number
US06495683B2

Reaction notes

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