Trifluoroacetic acid → HCID 178513109, compound

HRID 1021329Notes

Reaction equation

HRID 1021329 reaction equation
[C:1]([O:5][C:6]1[N:11]=[CH:10][C:9]([O:12][CH:13]2[CH2:16][N:15]([C:17]3[C:18](F)=[C:19](CO)[CH:20]=[CH:21][CH:22]=3)[CH2:14]2)=[CH:8][CH:7]=1)(C)(C)C.[CH:26]1N=CN(C(N2C=NC=C2)=[O:32])C=1.[C:38](=[O:41])([OH:40])[OH:39].[NH2:42][C:43]([NH2:45])=[NH:44].[C:46]([OH:52])([C:48](F)(F)F)=[O:47]>ClCCl.CN(C=O)C>[C:38]([C@@H:1]([C@H:48]([C:46]([OH:52])=[O:47])[OH:32])[OH:5])([OH:40])=[O:41].[C:43]([NH:45][C:38](=[O:41])[O:39][CH:17]([N:15]1[CH2:14][CH:13]([O:12][C:9]2[CH:8]=[CH:7][C:6](=[O:5])[NH:11][CH:10]=2)[CH2:16]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:26]=1)(=[NH:42])[NH2:44]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 286947Carbonic acid-guanidine (1:1)HCID 68310271HCID 68310271, compound

Product 1

HCID 178513109HCID 178513109, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of (3-{3-[(6-tert-butoxypyridin-3-yl)oxy]azetidin-1-yl}-2-fluorophenyl)methanol (120 mg) and DMF (2 ml) was added CDI (130 mg), followed by stirring at room temperature for 3 hours. To the reaction mixture was added guanidine carbonate (260 mg), followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, water and CHCl3 were added thereto, and the organic layer was dried over anhydrous sodium sulfate. After concentrating under reduced pressure, the obtained residue was purified by silica gel column chromatography (CHCl3/MeOH). The purified product thus obtained was mixed with dichloromethane (2 ml), and TFA (0.5 ml) was added thereto, followed by stirring at room temperature overnight. The reaction solution was concentrated under reduced pressure, and a saturated aqueous sodium hydrogen carbonate solution and CHCl3 were then added thereto. The organic layer was dried over Na2SO4 and then concentrated under reduced pressure. The obtained residue was mixed with a mixed solution of MeCN and H2O at 95:5, and L-tartaric acid (41 mg) was added thereto, followed by stirring at room temperature for 1 hour. The solid was collected by filtration to obtain 2-fluoro-3-({3-[(6-oxo-1,6-dihydropyridin-3-yl)oxy]azetidin-1-yl}benzyl carbamimidoylcarbamate L-tartrate (118 mg).

Workup

  1. stirringby stirring at room temperature for 1 hour
  2. concentrationThe reaction mixture was concentrated under reduced pressure, water and CHCl3
  3. additionwere added
  4. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  5. concentrationAfter concentrating under reduced pressure
  6. customthe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)
  7. customThe purified product thus obtained
  8. additionwas added
  9. stirringby stirring at room temperature overnight
  10. concentrationThe reaction solution was concentrated under reduced pressure
  11. additiona saturated aqueous sodium hydrogen carbonate solution and CHCl3 were then added
  12. dry with materialThe organic layer was dried over Na2SO4
  13. concentrationconcentrated under reduced pressure
  14. additionThe obtained residue was mixed with a mixed solution of MeCN and H2O at 95:5, and L-tartaric acid (41 mg)
  15. additionwas added
  16. stirringby stirring at room temperature for 1 hour
  17. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-8d12b7af7e65440188cbf33962d15eb4
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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