Diisopropylethylamine → Methyl(1RS,2SR)-2-(6-(4-((4-chlorobenzyl)oxy)-2-oxopyridin-1(2H)-yl)-1-methyl-1H-benzimidazol-2-yl)cyclobutanecarboxylate

HRID 2203053Notes

Reaction equation

HRID 2203053 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)=[CH:10][C:9]2=[O:23])=[CH:4][C:3]=1[NH:24][CH3:25].[CH3:26][O:27][C:28]([CH:30]1[CH2:33][CH2:32][CH:31]1[C:34](O)=O)=[O:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Cl:22][C:19]1[CH:18]=[CH:17][C:16]([CH2:15][O:14][C:11]2[CH:12]=[CH:13][N:8]([C:5]3[CH:6]=[CH:7][C:2]4[N:1]=[C:34]([CH:31]5[CH2:32][CH2:33][CH:30]5[C:28]([O:27][CH3:26])=[O:29])[N:24]([CH3:25])[C:3]=4[CH:4]=3)[C:9](=[O:23])[CH:10]=2)=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2818912-(methoxycarbonyl)cyclobutanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896902584-(4-Chlorobenzyloxy)-1-(4-amino-3-(methylamino)phenyl)pyridin-2(1h)-one

Product 1

HCID 121386218Methyl(1RS,2SR)-2-(6-(4-((4-chlorobenzyl)oxy)-2-oxopyridin-1(2H)-yl)-1-methyl-1H-benzimidazol-2-yl)cyclobutanecarboxylateYield 15.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(4-amino-3-(methylamino)phenyl)-4-((4-chlorobenzyl)oxy)pyridin-2(1H)-one (830 mg), (1RS, 2SR)-2-(methoxycarbonyl)cyclobutanecarboxylic acid (406 mg), HATU (1.33 g), N,N-diisopropylethylamine (0.611 ml) and DMF (20 ml) was stirred at room temperature for 2 h. The mixture was quenched with water, and extracted with EtOAc. The organic layer was separated, washed with water and brine successively, dried over MgSO4 and concentrated in vacuo. Then a mixture of the obtained residue and AcOH (20 ml) was stirred at 80° C. for 30 min. After concentration of the mixture, the residue was poured into saturated NaHCO3 solution, and extracted with EtOAc. The organic layer was separated, washed with water and brine successively, dried over MgSO4, and concentrated in vacuo. The residual solid was washed with IPE to give the title compound (172 mg) as a brown solid.

Workup

  1. customThe mixture was quenched with water
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed with water and brine successively
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. additionThen a mixture of the obtained residue and AcOH (20 ml)
  8. stirringwas stirred at 80° C. for 30 min
  9. additionAfter concentration of the mixture, the residue was poured into saturated NaHCO3 solution
  10. extractionextracted with EtOAc
  11. customThe organic layer was separated
  12. washwashed with water and brine successively
  13. dry with materialdried over MgSO4
  14. concentrationconcentrated in vacuo
  15. washThe residual solid was washed with IPE

Sources & evidence

ORD record
ord-265455b216f541748abca57233790fb2
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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