Trifluoroacetic acid → HCID 178512533, compound

HRID 1497561Notes

Reaction equation

HRID 1497561 reaction equation
C(OC([NH:8][C:9](=[N:55]C(OC(C)(C)C)=O)[NH:10][C:11]1[CH:54]=[CH:53][C:14]([C:15]([O:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[N:24]=[C:23]([C:28]([N:30]([CH2:39][C:40]2[CH:41]=[C:42]([CH:50]=[CH:51][CH:52]=2)[C:43]([O:45]C(C)(C)C)=[O:44])[CH2:31][C:32]([O:34]C(C)(C)C)=[O:33])=[O:29])[CH:22]=[CH:21]3)=[O:16])=[CH:13][CH:12]=1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH:10]([C:11]1[CH:12]=[CH:13][C:14]([C:15]([O:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[N:24]=[C:23]([C:28]([N:30]([CH2:39][C:40]2[CH:41]=[C:42]([CH:50]=[CH:51][CH:52]=2)[C:43]([OH:45])=[O:44])[CH2:31][C:32]([OH:34])=[O:33])=[O:29])[CH:22]=[CH:21]3)=[O:16])=[CH:53][CH:54]=1)[C:9]([NH2:55])=[NH:8]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178451240HCID 178451240, compound

Product 1

HCID 178512533HCID 178512533, compoundYield 56.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 3-{[{[6-({4-[N′,N″-bis(tert-butoxycarbonyl)carbamimidamido]benzoyl}oxy)quinolin-2-yl]carbonyl}(2-tert-butoxy-2-oxoethyl)amino]methyl}benzoate (659 mg) in dichloromethane (5.00 mL) was added trifluoroacetic acid (2.40 mL), followed by stirring at room temperature overnight. The reaction solution was concentrated under reduced pressure, and then to the residue was added acetonitrile (20.0 mL), followed by concentrating under reduced pressure again. This operation was repeated twice, and then acetonitrile (20.0 mL) was added thereto, followed by stirring at room temperature for 1 hour, and further heating and refluxing at 100° C. for 2 hours. The reaction solution was ice-cooled, and then 1 M sodium hydroxide (1.54 mL) was added thereto. Subsequently, a saturated aqueous sodium hydrogen carbonate solution was added thereto to adjust the pH to around 5. After stirring for 1 hour under ice-cooling, the insoluble matter was collected by filtration, and the filtrate was washed with a 50% aqueous acetonitrile solution and then dried at 50° C. for under reduced pressure. The dried product (354 mg) was suspended in a 33% aqueous acetonitrile solution (9.00 mL), and then methane sulfonic acid (0.100 mL) was added thereto. After stirring at 60° C. for 30 minutes, water (6.00 mL) was added thereto, followed by stirring at room temperature overnight. The precipitated crystals were collected by filtration, washed with a 10% aqueous acetonitrile solution, and then dried under reduced pressure to obtain 3-{[({6-[(4-carbamimidamidobenzoyl)oxy]quinolin-2-yl}carbonyl)(carboxymethyl)amino]methyl}benzoic acid (236 mg).

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. additionto the residue was added acetonitrile (20.0 mL)
  3. concentrationby concentrating under reduced pressure again
  4. additionacetonitrile (20.0 mL) was added
  5. stirringby stirring at room temperature for 1 hour
  6. temperaturefurther heating
  7. temperaturerefluxing at 100° C. for 2 hours
  8. temperaturecooled
  9. addition1 M sodium hydroxide (1.54 mL) was added
  10. additionSubsequently, a saturated aqueous sodium hydrogen carbonate solution was added
  11. stirringAfter stirring for 1 hour under ice-
  12. temperaturecooling
  13. filtrationthe insoluble matter was collected by filtration
  14. washthe filtrate was washed with a 50% aqueous acetonitrile solution
  15. customdried at 50° C. for under reduced pressure
  16. additionmethane sulfonic acid (0.100 mL) was added
  17. stirringAfter stirring at 60° C. for 30 minutes
  18. additionwater (6.00 mL) was added
  19. stirringby stirring at room temperature overnight
  20. filtrationThe precipitated crystals were collected by filtration
  21. washwashed with a 10% aqueous acetonitrile solution
  22. customdried under reduced pressure

Sources & evidence

ORD record
ord-e4970c65def0405ea3b69f3a0d5cd54d
Source dataset
uspto-grants-2015_12
Patent number
US09199927B2

Reaction notes

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