Piperidine → 1-(3,5-Dichloro-pyridin-4-ylmethyl)-6-methoxy-4-phenylethynyl-phthalazine

HRID 2297432Notes

Reaction equation

HRID 2297432 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5]([CH2:14][C:15]2[C:20]([Cl:21])=[CH:19][N:18]=[CH:17][C:16]=2[Cl:22])=[N:4][N:3]=1.N1CCCCC1.[C:29]1([C:35]#[CH:36])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.Cl[Pd]Cl.[Cu]I>[Cl:22][C:16]1[CH:17]=[N:18][CH:19]=[C:20]([Cl:21])[C:15]=1[CH2:14][C:5]1[C:6]2[C:11](=[CH:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=2)[C:2]([C:36]#[C:35][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[N:3][N:4]=1

Participants

8

Reactant 4

HCID 8082PiperidineHCID 10821PhenylacetyleneHCID 11776TriphenylphosphineHCID 186292104-Chloro-1-[(3,5-dichloropyridin-4-yl)methyl]-6-methoxyphthalazine

Product 1

HCID 99538911-(3,5-Dichloro-pyridin-4-ylmethyl)-6-methoxy-4-phenylethynyl-phthalazineYield 65%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-chloro-1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazine (0.52 g, 1.5 mmoles), prepared as described in example 45, in dry DMF (10 ml) under N2 was added with piperidine (1 ml, 10 mmoles), phenylacetylene (0.15 g, 1.5 mmoles), PdCl2 (0.013 g, 0.075 mmole), triphenylphosphine (0.039 g, 0.15 mmole) and CuI (0.014 g, 0.075 mmole). The mixture was stirred for 20 hours, poured into saturated NHCl (10 volumes) and extracted twice with CH2Cl2, then washed with 5% HCl, anhydrified and concentrated to give a solid which was flash chromatographed (eluent: CH2Cl2/ethyl ether 9:1). The resultant solid was triturated in ethyl ether to give 0.41 g of the title compound (yield: 52%). m.p.: 213.4-214.4° C. (dec.).

Workup

  1. additionpoured into saturated NHCl (10 volumes)
  2. extractionextracted twice with CH2Cl2
  3. washwashed with 5% HCl, anhydrified
  4. concentrationconcentrated
  5. customto give a solid which
  6. customchromatographed (eluent: CH2Cl2/ethyl ether 9:1)
  7. customThe resultant solid was triturated in ethyl ether

Sources & evidence

ORD record
ord-a94f40caf3a9467bb250ea3a477896fb
Source dataset
uspto-grants-2002_12
Patent number
US06492360B1

Reaction notes

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