Dimethylformamide → Methyl 3-[2-(2,6-dichlorophenyl)-6-quinolinyl]-2-{[3,4-dioxo-2-(propylamino)-1-cyclobuten-1-yl]amino}propanoate

HRID 1869809Notes

Reaction equation

HRID 1869809 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH2:19][CH:20]([NH:25][C:26]3[C:29](=[O:30])[C:28](=[O:31])[C:27]=3OC(C)C)[C:21]([O:23][CH3:24])=[O:22])[CH:15]=2)[N:10]=1.[CH2:36]([NH2:39])[CH2:37][CH3:38].CN(C=O)C>CO.O>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH2:19][CH:20]([NH:25][C:26]3[C:29](=[O:30])[C:28](=[O:31])[C:27]=3[NH:39][CH2:36][CH2:37][CH3:38])[C:21]([O:23][CH3:24])=[O:22])[CH:15]=2)[N:10]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 7852PropylamineHCID 57987604Methyl 3-[2-(2,6-dichlorophenyl)-6-quinolinyl]-2-[(2-isopropoxy-3,4-dioxo-1-cyclobuten-1-yl)amino]propanoate

Product 1

HCID 57987645Methyl 3-[2-(2,6-dichlorophenyl)-6-quinolinyl]-2-{[3,4-dioxo-2-(propylamino)-1-cyclobuten-1-yl]amino}propanoateYield 10%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

To methyl 3-[2-(2,6-dichlorophenyl)-6-quinolinyl]-2-[(2-isopropoxy-3,4-dioxo-1-cyclobuten-1-yl)amino]propanoate 116 (690 mg) in CH3OH (20 ml) are added 132 μl of n-propylamine. After addition of DMF (15 ml), the solution is stirred at RT overnight. The evaporation of CH3OH gives a DMF residue that is diluted in water (200 ml) and stirred overnight. The solid is filtered, washed with water then with MeOH, diluted in DMF, and n-propylamine (150 μl) is added to drive the reaction to completion. The solution is stirred at RT for 48 h, then poured into water. DMF is evaporated and the resulting solid is filtered, washed with water and dried. The product is purified by HPLC/MS (eluent: CH3CN/water/TFA, 8 minutes gradient from respectively 5/95/0.1 to 95/5/0.1). CH3CN is evaporated and water is added to the residue. The resulting solid is filtered and dried to give methyl 3-[2-(2,6-dichlorophenyl)-6-quinolinyl]-2-{[3,4-dioxo-2-(propylamino)-1-cyclobuten-1-yl]amino}propanoate 123.

Workup

  1. customThe evaporation of CH3OH
  2. customgives a DMF residue that
  3. stirringstirred overnight
  4. filtrationThe solid is filtered
  5. washwashed with water
  6. additionwith MeOH, diluted in DMF
  7. additionn-propylamine (150 μl) is added
  8. customthe reaction to completion
  9. stirringThe solution is stirred at RT for 48 h
  10. customDMF is evaporated
  11. filtrationthe resulting solid is filtered
  12. washwashed with water
  13. customdried
  14. customThe product is purified by HPLC/MS (eluent
  15. customCH3CN/water/TFA, 8 minutes
  16. customCH3CN is evaporated
  17. additionwater is added to the residue
  18. filtrationThe resulting solid is filtered
  19. customdried

Sources & evidence

ORD record
ord-828f112117604f17a6d3b0ba7bdb69df
Source dataset
uspto-grants-2009_12
Patent number
US07638630B2

Reaction notes

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