HCID 10237594, compound → N-(4-Chlorobenzyl)-2-(4-hydroxy-4-phenyl-1-butyn-1-yl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide

HRID 1814895Notes

Reaction equation

HRID 1814895 reaction equation
Br[C:2]1[O:23][C:5]2[N:6]([CH3:22])[CH:7]=[C:8]([C:11]([NH:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)=[O:12])[C:9](=[O:10])[C:4]=2[CH:3]=1.[C:24]1([CH:30]([OH:34])[CH2:31][C:32]#[CH:33])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(N(CC)CC)C.CN(C=O)C.[Cu]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:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][NH:13][C:11]([C:8]2[C:9](=[O:10])[C:4]3[CH:3]=[C:2]([C:33]#[C:32][CH2:31][CH:30]([OH:34])[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[O:23][C:5]=3[N:6]([CH3:22])[CH:7]=2)=[O:12])=[CH:16][CH:17]=1

Participants

7

Reactant 2

HCID 10237594HCID 10237594, compoundHCID 110190061-phenylbut-3-yn-1-ol

Product 1

HCID 10195313N-(4-Chlorobenzyl)-2-(4-hydroxy-4-phenyl-1-butyn-1-yl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

2-Bromo-N-(4-chlorobenzyl)-7-methyl-4-oxo-4,7-dlhydrofuro[2,3-b]-pyridine-5-carboxamide (Example 79, 0.593 g) was suspended in a mixture of triethylamine (15 mL) and DMF (3 mL). CuI (0.029 g), Pd(PPh3)2Cl2 (0.105 g), and then 1-phenyl-3-butyn-1-ol (0.36 mL) were added. The reaction mixture was stirred at room temperature for 20 min and then was partitioned between CH2Cl2 (50 mL) and water (50 mL). The aqueous layer was separated and extracted with CH2Cl2 (3×50 mL). The combined organic layers were washed with a sat. aq. ammonium chloride solution (100 mL), dried (MgSO4), filtered and concentrated in vacuo. The resulting solid was purified by column chromatography (CH2Cl2/methanol; 99/1, 98/2) followed by recrystallization from methanol to yield 0.275 g of the title compound as a yellow solid. Physical characteristics. M.p. 202-203° C. (dec); 1H NMR (400 MHz, DMSO-d6) δ 10.50, 8.58, 7.44-7.25, 7.15, 5.73, 4.85-4.81, 4.55, 3.91, 2.89; MS (ESI+) m/z 461 (M+H)+.

Workup

  1. customwas partitioned between CH2Cl2 (50 mL) and water (50 mL)
  2. customThe aqueous layer was separated
  3. extractionextracted with CH2Cl2 (3×50 mL)
  4. washThe combined organic layers were washed with a sat. aq. ammonium chloride solution (100 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting solid was purified by column chromatography (CH2Cl2/methanol; 99/1, 98/2)
  9. customfollowed by recrystallization from methanol

Sources & evidence

ORD record
ord-8d3912f18666475d9af65759fd9ccb98
Source dataset
uspto-grants-2005_04
Patent number
US06878705B2

Reaction notes

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