Propargyl alcohol → N-[3-(3-Hydroxy-prop-1-ynyl)-benzyloxy]-2-[(pyridin-4-ylmethyl)-amino]-benzamide

HRID 1663131Notes

Reaction equation

HRID 1663131 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][CH:26]=1)[CH2:5][O:6][NH:7][C:8](=[O:23])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][CH2:16][C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1.[CH2:27]([OH:30])[C:28]#[CH:29].C(N(CC)CC)C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.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>[OH:30][CH2:27][C:28]#[C:29][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][CH:26]=1)[CH2:5][O:6][NH:7][C:8](=[O:23])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][CH2:16][C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1

Participants

8

Reactant 3

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 58989772N-(3-Iodo-benzyloxy)-2-[(pyridin-4-ylmethyl)-amino]-benzamide

Product 1

HCID 11749533N-[3-(3-Hydroxy-prop-1-ynyl)-benzyloxy]-2-[(pyridin-4-ylmethyl)-amino]-benzamide

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

N-(3-Iodo-benzyloxy)-2-[(pyridin-4-ylmethyl)-amino]-benzamide (example 361, 300 mg), propargyl alcohol (69 mg), CuI (19 mg), PdCl2(PPh3)2 (22 mg) and tetrabutylammonium iodide (241 mg) was dissolved in DMF (4 ml) and triethylamine (0.5 ml) was added drop-wise (exothermic reaction). The reaction mixture was stirred at room temperature for 30 minutes and partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with brine, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by chromatography on silica gel (EtOAc as eluent) and gave the title compound. 13C-NMR (DMSO-d6) δ 167.2, 149.5, 148.9, 148.3, 136.6, 132.5, 131.5, 130.9, 128.7, 128.6, 128.0, 122.3, 114.8, 113.3, 111.5, 90.0, 83.3, 76.3, 49.3, 44.8.

Workup

  1. customdrop-wise (exothermic reaction)
  2. custompartitioned between EtOAc and water
  3. extractionThe aqueous phase was extracted with EtOAc
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated under reduced pressure
  7. customThe residue was purified by chromatography on silica gel (EtOAc as eluent)

Sources & evidence

ORD record
ord-dad01d0dde934007b11d881acb8b4e2b
Source dataset
uspto-grants-2011_10
Patent number
US08034811B2

Reaction notes

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