Dimethylformamide → Diisopropylether ethyl acetate

HRID 724950Notes

Reaction equation

HRID 724950 reaction equation
N1C2C(=N[C:7](=[O:16])[C:8]3[CH:15]=[CH:14]C=NC=3N=2)C=CC=1.I[C:18]1[CH:19]=NN[CH:22]=1.C(N(CC)CC)C.CN(C)C=[O:33]>C(OCC)(=O)C.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.[Cu]I>[C:19]([O:16][CH2:7][CH3:8])(=[O:33])[CH3:18].[CH:18]([O:33][CH:15]([CH3:14])[CH3:8])([CH3:19])[CH3:22]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 770224-IodopyrazoleHCID 23119574HCID 23119574, compound

Product 1

HCID 22281796Diisopropylether ethyl acetate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5,11-dihydro-11-ethyl-8-ethynyl-4-methyl-(-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (obtained by procedures analogous to those described in Example 51) (147 mg), 4-iodopyrazole (199 mg), bis(triphenylphosphine)palladium(II) chloride (22 mg), copper(I) iodide (21 mg), and triethylamine (2 mL) in 4 mL of N,N-dimethylformamide was heated at 100° C. in a sealed tube for 40 min. The reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was dried over sodium sulfate and concentrated. The crude residue was dissolved in 60 mL of methanol and hydrogenated at 50 p.s.i. over 10% palladium on carbon (70 mg). After 24 hours, the reaction mixture was filtered and concentrated. The residue was purified by flash chromatography, eluting with methanol/ethyl acetate, to afford the compound of Example 52, m.p. 184°-187° C. (ethyl acetate/isopropyl ether), and the compound of Example 53, m.p. 199°-201° C. (ethyl acetate/hexanes).

Workup

  1. customobtained by procedures analogous to
  2. washwashed with water
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. dissolutionThe crude residue was dissolved in 60 mL of methanol
  6. filtrationthe reaction mixture was filtered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography
  9. washeluting with methanol/ethyl acetate

Sources & evidence

ORD record
ord-a283e6e6a10345d49e1fa2d552a69599
Source dataset
uspto-grants-1998_01
Patent number
US05705499

Reaction notes

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