Lithium Hydroxide → 2-(6-(1-((S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinoline-7-carboxylic acid

HRID 338862Notes

Reaction equation

HRID 338862 reaction equation
[F:1][C:2]([F:26])([F:25])[CH:3]([N:12]1[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:13]1)[C:4]1[CH:5]=[N:6][C:7]([NH:10][NH2:11])=[CH:8][CH:9]=1.[CH:27]([C:29]1[CH:38]=[CH:37][C:36]2[C:31](=[CH:32][C:33]([C:39]([O:41]C)=[O:40])=[CH:34][CH:35]=2)[N:30]=1)=O.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.C(=O)(O)[O-].[Na+].[Li+].[OH-]>CCO.C1COCC1.CCOCC.C(OCC)(=O)C>[C:20]([O:19][C:18]([NH:17][C@H:14]1[CH2:15][CH2:16][N:12]([CH:3]([C:4]2[CH:9]=[CH:8][C:7]3[N:6]([C:27]([C:29]4[CH:38]=[CH:37][C:36]5[C:31](=[CH:32][C:33]([C:39]([OH:41])=[O:40])=[CH:34][CH:35]=5)[N:30]=4)=[N:11][N:10]=3)[CH:5]=2)[C:2]([F:25])([F:1])[F:26])[CH2:13]1)=[O:24])([CH3:22])([CH3:23])[CH3:21]

Participants

10

Reactant 5

HCID 3939Lithium HydroxideHCID 516892Sodium BicarbonateHCID 12217721Iodo benzene diacetateHCID 86707403tert-butyl (3S)-1-(2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamateHCID 86707420Methyl 2-formylquinoline-7-carboxylate

Product 1

HCID 709845972-(6-(1-((S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinoline-7-carboxylic acidYield 78.5%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl (3S)-1-(2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate (Example 1, Step D; 0.46 g, 1.03 mmol) and methyl 2-formylquinoline-7-carboxylate (0.22 g, 1.03 mmol) in EtOH (10 mL) was stirred at ambient temperature for 1 hour. The solvent was removed under reduced pressure. The residue was dissolved in DCM (10 mL) and iodo benzene diacetate (0.40 g, 1.24 mmol) was added. The mixture was stirred at ambient temperature for 1 hour. Ethyl acetate (20 mL) and saturated sodium bicarbonate (10 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue obtained was dissolved in THF (5 mL) and 2 N LiOH (5.15 mL, 10.30 mmol) was added. The mixture was stirred at ambient temperature for 6 hours. Ether (20 mL) was added. The aqueous layer was separated and acidified with saturated potassium hydrogen sulfate to about pH 3. The resulting solid was collected by filtration to give 2-(6-(1-((S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinoline-7-carboxylic acid (0.45 g, 78.5%) as a solid.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in DCM (10 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue obtained
  9. stirringThe mixture was stirred at ambient temperature for 6 hours
  10. customThe aqueous layer was separated
  11. filtrationThe resulting solid was collected by filtration

Sources & evidence

ORD record
ord-8a60f1f95e5741f7b39ce5247af7de02
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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