Hydrochloric Acid → Benzyl-{3-[1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazin-5-yl]-prop-2-ynyl}-methyl-amine dihydrochloride

HRID 2268881Notes

Reaction equation

HRID 2268881 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:29])[C:7]=1[CH2:8][C:9]1[C:18]2[C:13](=[C:14](OS(C(F)(F)F)(=O)=O)[C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[CH:12]=[N:11][N:10]=1.[CH2:30]([N:37]([CH3:41])[CH2:38][C:39]#[CH:40])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(NCC)C.[ClH:47]>C(Cl)Cl.CO.C(OCC)(=O)C.C(Cl)Cl.[Cu]I>[ClH:1].[ClH:47].[CH2:30]([N:37]([CH2:38][C:39]#[C:40][C:14]1[C:15]([O:19][CH3:20])=[CH:16][CH:17]=[C:18]2[C:13]=1[CH:12]=[N:11][N:10]=[C:9]2[CH2:8][C:7]1[C:2]([Cl:1])=[CH:3][N:4]=[CH:5][C:6]=1[Cl:29])[CH3:41])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 4688PargylineHCID 8021DiethylamineHCID 53981658Trifluoro-methanesulfonic acid 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazin-5-yl ester

Product 1

HCID 18381694Benzyl-{3-[1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazin-5-yl]-prop-2-ynyl}-methyl-amine dihydrochlorideYield 83%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A suspension under N2 of trifluoro-methanesulfonic acid 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazin-5-yl ester (5 g, 10.68 mmoles), prepared as described in example 73, benzyl-methyl-prop-2-ynyl-amine (2.16 ml, 12.82 mmoles) and diethylamine (100 ml) was added under stirring with bis(triphenylphosphine)PdCl2 (150.2 mg, 0.214 mmole) and CuI (40.75 mg, 0.214 mmole). The mixture was refluxed for 6 hours, brought to dryness and the residue flash chromatographed (eluent: ethyl acetate) to give a solid which was dissolved in CH2Cl2/CH3OH 1:1 (50 ml), acidified with a solution of HCl in ethyl acetate and brought to dryness. The residue was dissolved in CH2Cl2 (100 ml), brought to dryness again, triturated in ethyl acetate (150 ml), filtered and dried in oven under vacuum at 40° C. to give 5.22 g of the title compound (yield: 83%).

Workup

  1. additionwas added
  2. temperatureThe mixture was refluxed for 6 hours
  3. customthe residue flash chromatographed (eluent: ethyl acetate)
  4. customto give a solid which
  5. customtriturated in ethyl acetate (150 ml)
  6. filtrationfiltered
  7. customdried in oven under vacuum at 40° C.

Sources & evidence

ORD record
ord-4fc41ffb1e344edebd89a4a7f4f98433
Source dataset
uspto-grants-2001_12
Patent number
US06329370B1

Reaction notes

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