Dimethylformamide → HCID 11786962, compound

HRID 1989877Notes

Reaction equation

HRID 1989877 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[C:17]([C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=4)=[CH:18][CH:19]=[CH:20][CH:21]=3)=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:32]([O-:35])([O-:34])=O.[Na+].[Na+].CN([CH:41]=[O:42])C>>[C:22]1([CH:17]([N:4]2[CH2:5][CH2:6][N:1]([C:7]3[CH:8]=[CH:9][C:10]([NH:13][C:14]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:29])([F:31])[F:30])=[CH:24][CH:23]=4)=[O:15])=[CH:11][CH:12]=3)[CH2:2][CH2:3]2)[C:32]([O:35][CH2:16][C:14]([O:42][CH3:41])=[O:15])=[O:34])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 10340Sodium CarbonateHCID 112010994'-Trifluoromethyl-biphenyl-2-carboxylic acid [4-(piperazinyl)-phenyl]-amide

Product 1

HCID 11786962HCID 11786962, compound

Procedure

A mixture of intermediate (2) (0.0117 mol) and Na2CO3 (0.0141 mol) in DMF (100 ml) was stirred at room temperature. A solution of intermediate (43) (0.0141 mol) in DMF (80 ml) was added dropwise. The mixture was stirred at room temperature for 20 hours. The solvent was evaporated. The residue was stirred in DCM (150 ml). The organic layer was washed with water, washed with a saturated NaHCO3 solution and washed with water. The combined organic layer was dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 99/1). The desired fractions were collected and the solvent was evaporated. The residue was stirred in DIPE (150 ml). The mixture was warmed up to reflux and 2-propanol (30 ml) and DCM (5 ml) was added. The mixture was stirred and refluxed until complete dissolution, then brought to room temperature. The mixture was stirred at room temperature for 60 hours. The precipitate was filtered off and dried in vacuo at 50° C., yielding 3.32 g of 2-methoxy-2-oxoethyl α-phenyl-4-[4-[[[4′-(trifluoromethyl)[1,1′-biphenyl]-2-yl]carbonyl]amino]phenyl]-1-piperazineacetate (compound 14, mp. 106° C.).

Workup

  1. stirringThe mixture was stirred at room temperature for 20 hours
  2. customThe solvent was evaporated
  3. stirringThe residue was stirred in DCM (150 ml)
  4. washThe organic layer was washed with water
  5. washwashed with a saturated NaHCO3 solution
  6. washwashed with water
  7. customThe combined organic layer was dried
  8. filtrationfiltered
  9. customthe solvent was evaporated
  10. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 99/1)
  11. customThe desired fractions were collected
  12. customthe solvent was evaporated
  13. stirringThe residue was stirred in DIPE (150 ml)
  14. temperatureThe mixture was warmed up
  15. temperatureto reflux
  16. addition2-propanol (30 ml) and DCM (5 ml) was added
  17. stirringThe mixture was stirred
  18. temperaturerefluxed until complete dissolution
  19. custombrought to room temperature
  20. stirringThe mixture was stirred at room temperature for 60 hours
  21. filtrationThe precipitate was filtered off
  22. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-1416fbc599a14eafbae93f1c0a7be991
Source dataset
uspto-grants-2010_01
Patent number
US07642378B2

Reaction notes

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