Trifluoroacetic acid → HCID 117843747, compound

HRID 2209086Notes

Reaction equation

HRID 2209086 reaction equation
C(O)(C(F)(F)F)=O.[F:8][CH:9]([F:40])[N:10]1[C:14]2[C:15]([O:31][C@@H:32]([C@H:34]3[CH2:38][NH:37][C:36](=[O:39])[CH2:35]3)[CH3:33])=[N:16][C:17]([C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)=[CH:21][CH:20]=3)=[CH:18][C:13]=2[N:12]=[CH:11]1.CCN(C(C)C)C(C)C.[O:50]1[CH2:53][C:52](=O)[CH2:51]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.O.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>[F:40][CH:9]([F:8])[N:10]1[C:14]2[C:15]([O:31][C@@H:32]([C@H:34]3[CH2:38][NH:37][C:36](=[O:39])[CH2:35]3)[CH3:33])=[N:16][C:17]([C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][N:28]([CH:52]5[CH2:53][O:50][CH2:51]5)[CH2:27][CH2:26]4)=[CH:21][CH:20]=3)=[CH:18][C:13]=2[N:12]=[CH:11]1

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 117843082HCID 117843082, compound

Product 1

HCID 117843747HCID 117843747, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
52.5 °C

Procedure

The crude TFA salt of (R)-4-((R)-1-((3-(difluoromethyl)-6-(4-(piperazin-1-yl)phenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one: (3.63) (0.06 mmol) was dissolved in THF (1.05 mL) and iPr2NEt (11 μL, 0.063 mmol) was added followed by oxetan-3-one (15 μL, 0.26 mmol) and sodium triacetoxyborohydride (57 mg, 0.27 mmol). The reaction mixture was stirred at 50-55° C. for 3 h and was diluted with water, 5% (w/v) aqueous Na2CO3, and EtOAc. The phases were separated, and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, and concentrated to afford a crude residue that was purified by silica gel chromatography (0-25% MeOH in DCM) to yield (R)-4-((R)-1-((3-(difluoromethyl)-6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one: (3.66).

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with EtOAc
  3. dry with materialThe combined organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a crude residue that
  7. customwas purified by silica gel chromatography (0-25% MeOH in DCM)

Sources & evidence

ORD record
ord-fd664562e2ed41758404f938efafb342
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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