Trifluoroacetic acid → Trifluoroacetic acid

HRID 516136Notes

Reaction equation

HRID 516136 reaction equation
C(OC([NH:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([C:22]3[S:26][N:25]=[C:24]([CH3:27])[CH:23]=3)[C:19]3[C:28](=[O:38])[N:29](C(OC(C)(C)C)=O)[CH2:30][C:18]=3[C:17]=2[F:39])[CH2:13][CH2:12][O:11][CH2:10]1)=O)(C)(C)C.[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41]>C(Cl)Cl>[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41].[NH2:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([C:22]3[S:26][N:25]=[C:24]([CH3:27])[CH:23]=3)[C:19]3[C:28](=[O:38])[NH:29][CH2:30][C:18]=3[C:17]=2[F:39])[CH2:13][CH2:12][O:11][CH2:10]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67238495HCID 67238495, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 53251178HCID 53251178, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(3-methylisothiazol-5-yl)-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (5.5 mg, 9.76 μmol) in DCM (2.0 mL) was added TFA (2.0 mL, 26.0 mmol). The reaction mixture was stirred at RT for 1 h, and concentrated in vacuo. The resulting crude material was reconstituted in DMF and purified via preparative HPLC eluting with water (0.05% TFA) and ACN (55-80% gradient, 0.035% TFA). The collected fractions were combined and the ACN was removed via rotary evaporation. The resulting aq solution was neutralized with saturated aq NaHCO3, washed with EtOAc (2×50 mL), dried over anhydrous Na2SO4, filtered, and the organic phase stripped to dryness via rotary evaporation. The residue was recrystallized from THF/hexane to give a TFA salt of the title compound. [M+H] calc'd for C16H18FN5O2S, 364; found, 364.

Workup

  1. concentrationconcentrated in vacuo
  2. custompurified via preparative HPLC
  3. washeluting with water (0.05% TFA) and ACN (55-80% gradient, 0.035% TFA)
  4. customthe ACN was removed via rotary evaporation
  5. washwashed with EtOAc (2×50 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customthe organic phase stripped to dryness via rotary evaporation
  9. customThe residue was recrystallized from THF/hexane

Sources & evidence

ORD record
ord-488e0faf8ab64fdf904f4a9cabdb7388
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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