HCID 11550475, compound → HCID 66629483, compound

HRID 426376Notes

Reaction equation

HRID 426376 reaction equation
[C:1]([C:3]1[C:20]([C:21]#[N:22])=[CH:19][C:6]2[N:7](CCC)[C:8]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)=[N:9][C:5]=2[CH:4]=1)#[N:2].[CH2:23]([C:26](C1C=CC(C=O)=CC=1)([CH2:30][CH:31]=[CH2:32])[CH2:27][CH:28]=[CH2:29])[CH:24]=[CH2:25]>CN1C(=O)CCC1.C(OCC)(=O)C>[CH2:23]([C:26]([C:13]1[CH:14]=[CH:15][C:10]([C:8]2[NH:7][C:6]3[CH:19]=[C:20]([C:21]#[N:22])[C:3]([C:1]#[N:2])=[CH:4][C:5]=3[N:9]=2)=[CH:11][CH:12]=1)([CH2:30][CH:31]=[CH2:32])[CH2:27][CH:28]=[CH2:29])[CH:24]=[CH2:25]

Participants

5

Reactant 2

HCID 11550475HCID 11550475, compoundHCID 11709006HCID 11709006, compound

Product 1

HCID 66629483HCID 66629483, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
120 °C

Procedure

A solution of 1 (198 mg, 1.25 mmol) in NMP (2.5 mL) and a solution of 2 (300 mg, 1.25 mmol) in NMP (3.5 mL) were combined in a flask fitted with a Hickman still. The mixture was heated at 120° C. and stirred for 2 h. Then FeCl3.6H2O (17 mg, 63 μmol) was added and oxygen was bubbled through the mixture with continued heating and stirring for 20 h. The cooled reaction mixture was diluted with ethyl acetate. The organic solution was washed with water and brine. The organic layer was dried (Na2SO4), filtered, concentrated, and chromatographed (silica, CH2Cl2 w/ethyl acetate gradient of 0-5%). Fractions containing the desired compound were concentrated to give a reddish solid, which was chromatographed over a short plug of alumina (CH2Cl2 w/ethyl acetate gradient of 10-100%) yielding a colorless solid (268 mg, 57%): mp 264-266° C.; 1H NMR (d6-acetone) δ 2.57 (d, J=7.2 Hz, 6H), 4.88-5.11 (m, 6H), 5.56-5.69 (m, 3H), 7.65 (d, J=8.8 Hz, 2H), 8.26 (d, J=8.8 Hz, 2H), 12.89 (brs, 1H); 13C NMR (d6-acetone) δ 41.6, 44.0, 108.2, 116.9, 117.7, 126.4, 127.3, 128.0, 134.4, 150.2; FABMS obsd 379.1909, calcd 379.1923 (C25H22N4).

Workup

  1. customfitted with a Hickman still
  2. customoxygen was bubbled through the mixture
  3. temperaturewith continued heating
  4. stirringstirring for 20 h
  5. customThe cooled reaction mixture
  6. washThe organic solution was washed with water and brine
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customchromatographed (silica, CH2Cl2 w/ethyl acetate gradient of 0-5%)
  11. additionFractions containing the desired compound
  12. concentrationwere concentrated
  13. customto give a reddish solid, which
  14. customwas chromatographed over a short plug of alumina (CH2Cl2 w/ethyl acetate gradient of 10-100%)

Sources & evidence

ORD record
ord-5216cd57b97941f7adeeaf8959709377
Source dataset
uspto-grants-2012_01
Patent number
US08106393B2

Reaction notes

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