Ethyl Acetate → 3-[(Quinolin-4-ylmethyl)amino]thiophene-2-carboxylic acid [3-(2-methoxy-3,4-dioxocyclobut-1-enyl)phenyl]amide

HRID 1171899Notes

Reaction equation

HRID 1171899 reaction equation
[CH3:1][O:2][C:3]1[C:4](=[O:21])[C:5](=[O:20])[C:6]=1[Sn](CCCC)(CCCC)CCCC.I[C:23]1[CH:24]=[C:25]([NH:29][C:30]([C:32]2[S:33][CH:34]=[CH:35][C:36]=2[NH:37][CH2:38][C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[N:42]=[CH:41][CH:40]=2)=[O:31])[CH:26]=[CH:27][CH:28]=1.CCOC(C)=O>[Cu](I)I.C(Cl)Cl>[CH3:1][O:2][C:3]1[C:4](=[O:21])[C:5](=[O:20])[C:6]=1[C:27]1[CH:26]=[C:25]([NH:29][C:30]([C:32]2[S:33][CH:34]=[CH:35][C:36]=2[NH:37][CH2:38][C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[N:42]=[CH:41][CH:40]=2)=[O:31])[CH:24]=[CH:23][CH:28]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 586460293-Methoxy-4-tributylstannanylcyclobut-3-ene-1,2-dioneHCID 586460363-[(Quinolin-4-ylmethyl)amino]thiophene-2-carboxylic acid (3-iodophenyl)amide

Product 1

HCID 586460313-[(Quinolin-4-ylmethyl)amino]thiophene-2-carboxylic acid [3-(2-methoxy-3,4-dioxocyclobut-1-enyl)phenyl]amide

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6344DichloromethaneSolvent

Procedure

Nitrogen was bubbled through a solution containing 3-methoxy-4-tributylstannanylcyclobut-3-ene-1,2-dione (0.40 g, 1.0 mmol) and 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylic acid (3-iodophenyl)amide (0.54 g, 1.1 mmol) for 5 min, then benzylchlorobis(triphenyl phosphine)Pd(II) (45 mg, 0.06 mmol) and copper iodide (17 mg, 0.09 mmol) were added. The mixture stirred at rt for 1 h. EtOAc (50 mL) was added and the mixture was filtered, partitioned over saturated aqueous NH4Cl, and then washed with 10% aqueous KF solution. The aqueous layer was back-extracted with EtOAc (3×50 mL) and the combined organics were dried over MgSO4, filtered, and concentrated in vacuo. The mixture purified by silica gel chromatography (100% EtOAc) to yield a yellow oil. CH2Cl2 was added and the solution was sonicated. Title compound 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylic acid [3-(2-methoxy-3,4-dioxocyclobut-1-enyl)phenyl]amide precipitated out as a yellow solid and was filtered. MS (ES): m/z 470.0 [M+1]. 1H NMR (DMSO-d6, 400 MHz): δ=4.54 (s, 3H), 5.10 (d, J=6.4 Hz, 2H), 6.80 (d, J=3.2 Hz, 1H), 7.40 (d, J=4.0 Hz, 1H), 7.53 (t, J=7.2 Hz, 1H), 7.60-7.64 (m, 2H), 7.70 (t, J=8.0 Hz, 1H), 7.81 (t, J=8.0 Hz, 1H), 7.91 (d, J=8.4 Hz, 1H), 8.06 (d, J=8.08-8.12 (m, 1H), 8.32 (s, 1H), 8.85 (d, J=4.0 Hz, 1H), 9.75 (s, 1H).

Workup

  1. customNitrogen was bubbled through a solution
  2. filtrationthe mixture was filtered
  3. custompartitioned over saturated aqueous NH4Cl
  4. washwashed with 10% aqueous KF solution
  5. extractionThe aqueous layer was back-extracted with EtOAc (3×50 mL)
  6. dry with materialthe combined organics were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe mixture purified by silica gel chromatography (100% EtOAc)
  10. customto yield a yellow oil
  11. customthe solution was sonicated
  12. customTitle compound 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylic acid [3-(2-methoxy-3,4-dioxocyclobut-1-enyl)phenyl]amide precipitated out as a yellow solid
  13. filtrationwas filtered

Sources & evidence

ORD record
ord-c256af32c56643eda6a2a57816e515e0
Source dataset
uspto-grants-2010_11
Patent number
US07829717B2

Reaction notes

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