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

HRID 2268861Notes

Reaction equation

HRID 2268861 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.[NH4+].[Cl-]>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

9

Reactant 5

HCID 8082PiperidineHCID 10821PhenylacetyleneHCID 11776TriphenylphosphineHCID 25517Ammonium ChlorideHCID 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 NH4Cl (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. extractionextracted twice with CH2Cl2
  2. washwashed with 5% HCl, anhydrified
  3. concentrationconcentrated
  4. customto give a solid which
  5. customchromatographed (eluent: CH2Cl2/ethyl ether 9:1)
  6. customThe resultant solid was triturated in ethyl ether

Sources & evidence

ORD record
ord-68ed6467fd2e4edcac3e0e110879315b
Source dataset
uspto-grants-2001_12
Patent number
US06329370B1

Reaction notes

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