Hydrochloric Acid → HCID 178522936, compound

HRID 2299290Notes

Reaction equation

HRID 2299290 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:27])[CH2:24][C:25]#[CH:26].Cl>C(NCC)C.CN(C=O)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:26]#[C:25][CH2:24][CH2:23][OH:27])[S:16][C:13]3=[N:14][CH:15]=2)=[O:9])=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 135663-Butyn-1-OLHCID 178522942HCID 178522942, compound

Product 1

HCID 178522936HCID 178522936, compoundYield 21%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 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 3-butyn-1-ol (0.20 mL). The reaction is stirred at rt for 18 h. 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 dried with MgSO4, filtered, and concentrated in vacuo. The resulting brown oil is purified via column chromatography (CH2Cl2:CH3OH; 98:2). Fractions homogeneous by TLC are combined and concentrated in vacuo to yield a brown solid. This material is dissolved in DMF (15 mL) and 2N HCl is added until a precipitate forms. The resulting tan solid is purified via column chromatography (CH2Cl2:CH3OH; 98:2, 95:5). Fractions homogeneous by TLC are combined and concentrated in vacuo to yield 0.183 g (21 %) of the title compound as a yellow, crystalline 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. dry with materialCombined organic layers are dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting brown oil is purified via column chromatography (CH2Cl2:CH3OH; 98:2)
  8. concentrationconcentrated in vacuo
  9. customto yield a brown solid
  10. customThe resulting tan solid is purified via column chromatography (CH2Cl2:CH3OH; 98:2, 95:5)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-362235b78c1b410d87a4ab3e5eeface4
Source dataset
uspto-grants-2002_12
Patent number
US06495683B2

Reaction notes

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