Acetonitrile → 1-(3,5-Dichloro-pyridin-4-ylmethyl)-6-methoxy-5-(5-morpholin-4-yl-pent-1-ynyl)-phthalazine dihydrochloride

HRID 2268882Notes

Reaction equation

HRID 2268882 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:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1)[CH2:31][CH2:32][C:33]#[CH:34].C(NCC)C.C(#N)C>C(OCC)(=O)C.[Cu]I>[ClH:1].[ClH:1].[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]([C:34]#[C:33][CH2:32][CH2:31][CH2:30][N:35]3[CH2:36][CH2:37][O:38][CH2:39][CH2:40]3)[C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[CH:12]=[N:11][N:10]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 8021DiethylamineHCID 234379134-(Pent-4-YN-1-YL)morpholineHCID 53981658Trifluoro-methanesulfonic acid 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazin-5-yl ester

Product 1

HCID 183815961-(3,5-Dichloro-pyridin-4-ylmethyl)-6-methoxy-5-(5-morpholin-4-yl-pent-1-ynyl)-phthalazine dihydrochlorideYield 24.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

Trifluoromethanesulfonic acid 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazin-5-yl ester (0.935 g, 2 mmoles), prepared as described in example 73, 4-pent-4-ynyl-morpholine (0.37 g, 2.4 mmoles), diethylamine (9 ml) and dry acetonitrile (6 ml), then bis(triphenylphosphine)PdCl2 (0.014 g, 0.02 mmole) and CuI (0.004 g, 0.02 mmole) were charged in a flask under N2 and the mixture was stirred at room temperature overnight, brought to dryness, the residue taken up in ethyl acetate and washed with water. The organic phase was washed with water, anhydrified and concentrated to give an oil which was flash chromatographed (eluent: CH2Cl2/CH3OH/NH3 95:5:0.5) to give an oil which was dissolved in ethyl acetate and precipitated by adding HCl in ethyl ether. There was yielded 0.09 g of the title compound. m.p.: 129-13 1° C. (dec.).

Workup

  1. washwashed with water
  2. washThe organic phase was washed with water, anhydrified
  3. concentrationconcentrated
  4. customto give an oil which
  5. customchromatographed (eluent: CH2Cl2/CH3OH/NH3 95:5:0.5)
  6. customto give an oil which
  7. customprecipitated
  8. additionby adding HCl in ethyl ether

Sources & evidence

ORD record
ord-8a2b3dbbf2ea4d3eaf97628650d9e0b0
Source dataset
uspto-grants-2001_12
Patent number
US06329370B1

Reaction notes

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