Trifluoroacetic acid → HCID 71254008, compound

HRID 1775067Notes

Reaction equation

HRID 1775067 reaction equation
[CH3:1][N:2]1[CH:6](NC)[CH:5]([C:9]2[CH:10]=[C:11]3[C:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[N:16][N:15](C4CCCCO4)[C:12]3=[CH:13][N:14]=2)[CH2:4][C:3]1=[O:30].FC(F)(F)C(O)=O>>[CH3:1][N:2]1[CH2:6][C:5]([C:9]2[CH:10]=[C:11]3[C:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[N:16][NH:15][C:12]3=[CH:13][N:14]=2)=[CH:4][C:3]1=[O:30]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71253845HCID 71253845, compound

Product 1

HCID 71254008HCID 71254008, compoundYield 16.4%

Conditions

Temperature
105 °C

Procedure

A mixture of 1-methyl-5-(methylamino)-4-(3-phenyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrrolidin-2-one (34.3 mg, 0.084 mmol) and trifluoroacetic acid (3 mL) in a sealed high-pressure tube was stirred at 105° C. for 3 days. The reaction was cooled to RT and trifluoroacetic acid was removed via rotary evaporator. The resultant oil was diluted with ethyl acetate (30 mL). The organic layer was washed with aqueous saturated sodium bicarbonate solution (2×), water and brine, dried over Na2SO4, filtered, and evaporated in vacuo. The crude product was purified by reverse phase HPLC to give 259 as white solid (4.0 mg, 16.3%). 1H NMR (400 MHz, DMSO) δ 9.13 (s, 1H), 8.43 (s, 1H), 8.11 (d, J=7.5 Hz, 2H), 7.56 (t, J=7.6 Hz, 2H), 7.47 (d, J=7.3 Hz, 1H), 6.82 (s, 1H), 6.68 (s, 1H), 4.61 (s, 2H), 2.99 (s, 3H). LC/MS: m/z 291.0 [M+1]

Workup

  1. temperatureThe reaction was cooled to RT
  2. customtrifluoroacetic acid was removed via rotary evaporator
  3. additionThe resultant oil was diluted with ethyl acetate (30 mL)
  4. washThe organic layer was washed with aqueous saturated sodium bicarbonate solution (2×), water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-c2203959d5f14f85ab796812fc9c38c8
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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