3-Butyn-1-OL → HCID 491972, compound

HRID 1841540Notes

Reaction equation

HRID 1841540 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([CH2:21][CH:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:15][C:14]=3I)=[O:9])=[CH:4][CH:3]=1.[CH2:31]([OH:35])[CH2:32][C:33]#[CH:34]>N(CC)CC.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.[Cu]I>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13]4=[C:14]([CH:34]=[C:33]([CH2:32][CH2:31][OH:35])[N:12]4[CH:11]=2)[CH:15]=[C:16]([CH2:21][CH:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH:17]=3)=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 135663-Butyn-1-OLHCID 178522927HCID 178522927, compound

Product 1

HCID 491972HCID 491972, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8021DiethylamineSolvent

Procedure

A solution of N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(tetrahydro-2H-pyran-4-ylmethyl)-3-quinolinecarboxamide (0.16 g), PdCl2(PPh3)2, CuI (0.018 g) and 3-butyn-1-ol (0.03 mL) in 15 mL Et2NH is stirred at room temperature for 7 days. The solid in the reaction is filtered and rinsed with EtOAc. The filtrate is partitioned between EtOAc and H2O. The aqueous layer is extracted with EtOAc (3×). The organic layers and the solid previously filtered are combined, concentrated, adsorbed onto silica and chromatographed (gradient from CH2Cl2 to 4% MeOH in CH2Cl2). Product-containing fractions are combined and condensed to afford 101.6 mg (71%) of N-(4-chlorobenzyl)-2-(2-hydroxyethyl)-6-oxo-8-(tetrahydro-2H-pyran-4-ylmethyl)-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide as a tan solid.

Workup

  1. filtrationThe solid in the reaction is filtered
  2. washrinsed with EtOAc
  3. customThe filtrate is partitioned between EtOAc and H2O
  4. extractionThe aqueous layer is extracted with EtOAc (3×)
  5. filtrationThe organic layers and the solid previously filtered
  6. concentrationconcentrated
  7. customchromatographed (gradient from CH2Cl2 to 4% MeOH in CH2Cl2)
  8. customcondensed

Sources & evidence

ORD record
ord-d0a5427a349f432d86821072c7f1f785
Source dataset
uspto-grants-2004_01
Patent number
US06683181B2

Reaction notes

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