Hydrochloric Acid → (S)-1-((S)-1-(3-(7-ethoxy-6-fluoroquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-amine

HRID 339036Notes

Reaction equation

HRID 339036 reaction equation
[CH2:1]([O:3][C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][C:10]([C:14]3[N:18]4[CH:19]=[C:20]([C@H:23]([N:28]5[CH2:32][CH2:31][C@@:30]([NH:34]C(=O)OC(C)(C)C)([CH3:33])[CH2:29]5)[C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:22][C:17]4=[N:16][N:15]=3)=[N:11]2)=[CH:6][C:5]=1[F:42])[CH3:2].Cl.O1CCOCC1>C(Cl)Cl.O>[CH2:1]([O:3][C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][C:10]([C:14]3[N:18]4[CH:19]=[C:20]([C@H:23]([N:28]5[CH2:32][CH2:31][C@:30]([CH3:33])([NH2:34])[CH2:29]5)[C:24]([F:26])([F:25])[F:27])[CH:21]=[CH:22][C:17]4=[N:16][N:15]=3)=[N:11]2)=[CH:6][C:5]=1[F:42])[CH3:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86707532tert-butyl (S)-1-((S)-1-(3-(7-ethoxy-6-fluoro quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-ylcarbamate

Product 1

HCID 71004809(S)-1-((S)-1-(3-(7-ethoxy-6-fluoroquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-amineYield 92.05%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl (S)-1-((S)-1-(3-(7-ethoxy-6-fluoro quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-ylcarbamate (5.406 g, 9.185 mmol) in DCM (40 mL) was added 4M HCl in dioxane (22.96 mL, 91.85 mmol) and stirred at ambient temperature for 1.5 h. The filtered precipitate was dissolved in water and basified (1N NaOH), extracted with ethyl acetate (3×200 mL), washed with brine (200 mL), dried (MgSO4), filtered concentrated under reduced pressure and the residue purified by flash chromatography (1 column volume DCM, increasing to 10% methanol/DCM over 2 column volumes, holding for 3 column volumes, then switching to 10% [10% NH4OH/Methanol]/DCM for 7 column volumes) to give (S)-1-((S)-1-(3-(7-ethoxy-6-fluoroquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-amine (4.13 g, 8.45 mmol, 92.05% yield). MS APCI (+) m/z 489 (M+1) detected. Specific rotation: [α]20D=−0.87° (c=1.02, MeOH).

Workup

  1. extractionbasified (1N NaOH), extracted with ethyl acetate (3×200 mL)
  2. washwashed with brine (200 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customthe residue purified by flash chromatography (1 column volume DCM
  7. temperatureincreasing to 10% methanol/DCM over 2 column volumes

Sources & evidence

ORD record
ord-390de3ed46024e0f8e4d15d2c693dbde
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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