Diisopropylethylamine → HCID 59597009, compound

HRID 2265731Notes

Reaction equation

HRID 2265731 reaction equation
[NH2:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:19][CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.[F:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]([C:32]2([C:35](O)=[O:36])[CH2:34][CH2:33]2)=[O:31])=[CH:25][CH:24]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[N:16]1([C:14]([NH:13][C:9]2[CH:8]=[C:7]([O:6][C:5]3[CH:20]=[CH:21][C:2]([NH:1][C:35]([C:32]4([C:30]([NH:29][C:26]5[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=5)=[O:31])[CH2:34][CH2:33]4)=[O:36])=[CH:3][CH:4]=3)[CH:12]=[CH:11][N:10]=2)=[O:15])[CH2:19][CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic AcidHCID 59596945HCID 59596945, compound

Product 1

HCID 59597009HCID 59597009, compoundYield 8.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Azetidine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (108 mg) and 1-(4-fluorophenylcarbamoyl)cyclopropanecarboxylic acid (93.1 mg) were dissolved in N,N-dimethylformamide (4 ml), and diisopropylethylamine (0.363 ml) and HBTU (216 mg) were added under a nitrogen atmosphere at room temperature, followed by 3 hr. The reaction mixture was partitioned after addition of ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml). The separated organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml) and brine (30 ml), and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the resultant residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=1:7, then ethyl acetate). Fractions containing the target compound were concentrated under reduced pressure, and to the residue (106.2 mg) were added tert-butyl methyl ether (4 ml) and heptane (4 ml) to suspend a solid. The solid was collected by filtration, and dried under aeration to provide the roughly purified titled compound as pale yellow powder (87.5 mg). This was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=1:7, then ethyl acetate). Fractions containing the target compound were concentrated under reduced pressure, and to the residue were added tert-butyl methyl ether (4 ml) and heptane (2 ml) to suspend a solid. The solid was collected by filtration, and dried under aeration to provide white powder. The powder obtained by filtration and the filtrate were combined, and purified by LC-MS. The solution containing TFA, acetonitrile and water was concentrated under reduced pressure, and to the residue was added a saturated aqueous solution of sodium hydrogencarbonate (50 ml), followed by stirring. The solvent was removed under reduced pressure, and the residue was partitioned after addition of ethyl acetate (100 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml) and brine (50 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and to the residue were added tert-butyl methyl ether and heptane to suspend a solid. The solid was collected by filtration, and derided under aeration to provide the titled compound as a white powder (16.3 mg, 8.79%)

Workup

  1. customThe reaction mixture was partitioned
  2. additionafter addition of ethyl acetate (50 ml)
  3. washThe separated organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml) and brine (30 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe resultant residue was purified by silica gel column chromatography (eluent
  7. additionFractions containing the target compound
  8. concentrationwere concentrated under reduced pressure
  9. additionto the residue (106.2 mg) were added tert-butyl methyl ether (4 ml) and heptane (4 ml)
  10. filtrationThe solid was collected by filtration
  11. customdried under aeration
  12. customto provide the
  13. customroughly purified titled compound as pale yellow powder (87.5 mg)
  14. customThis was purified by silica gel column chromatography (eluent
  15. additionFractions containing the target compound
  16. concentrationwere concentrated under reduced pressure
  17. additionto the residue were added tert-butyl methyl ether (4 ml) and heptane (2 ml)
  18. filtrationThe solid was collected by filtration
  19. customdried under aeration
  20. customto provide white powder
  21. customThe powder obtained by filtration
  22. custompurified by LC-MS
  23. additionThe solution containing TFA, acetonitrile and water
  24. concentrationwas concentrated under reduced pressure
  25. additionto the residue was added a saturated aqueous solution of sodium hydrogencarbonate (50 ml)
  26. customThe solvent was removed under reduced pressure
  27. customthe residue was partitioned
  28. additionafter addition of ethyl acetate (100 ml)
  29. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml) and brine (50 ml) in this order
  30. dry with materialdried over anhydrous sodium sulfate
  31. customThe solvent was removed under reduced pressure
  32. additionto the residue were added tert-butyl methyl ether and heptane
  33. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-e876372aa0ec462981775ab77df336ef
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

Loading…