Propargyl alcohol → HCID 491951, compound

HRID 1060593Notes

Reaction equation

HRID 1060593 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:34])[C:32]#[CH:33]>C(NCC)C.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:33]=[C:32]([CH2:31][OH:34])[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 7859Propargyl alcoholHCID 178522927HCID 178522927, compound

Product 1

HCID 491951HCID 491951, compoundYield 56%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(tetrahydro-2H-pyran-4-ylmethyl)-3-quinolinecarboxamide (0.185 g), PdCl2(PPh3)2 (0.012 g), and CuI (0.032 g) in 10 mL of diethylamine is added propargyl alcohol (0.02 mL). The reaction is stirred overnight. The mixture is concentrated and the resulting solid is partitioned between CH2Cl2 and water. The aqueous layer is extracted with CH2Cl2 (3×). The combined organic layers are washed with brine, dried and condensed. The crude product is chromatographed (Biotage flash 40S, gradient from CH2Cl2 to 2% MeOH/CH2Cl2). Fractions homogeneous by TLC are combined and concentrated. The resulting solid is recrystallized from CH2Cl2/Et2O to yield 0.09 g (56%) of N-(4-chlorobenzyl)-2-(hydroxymethyl)-6-oxo-8-(tetrahydro-2H-pyran-4-ylmethyl)-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide as a white solid, m.p. 196-198° C.

Workup

  1. concentrationThe mixture is concentrated
  2. customthe resulting solid is partitioned between CH2Cl2 and water
  3. extractionThe aqueous layer is extracted with CH2Cl2 (3×)
  4. washThe combined organic layers are washed with brine
  5. customdried
  6. customcondensed
  7. customThe crude product is chromatographed (Biotage flash 40S, gradient from CH2Cl2 to 2% MeOH/CH2Cl2)
  8. concentrationconcentrated
  9. customThe resulting solid is recrystallized from CH2Cl2/Et2O

Sources & evidence

ORD record
ord-2274fa98f5d34501a8c2903670bf2516
Source dataset
uspto-grants-2003_02
Patent number
US06525049B2

Reaction notes

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