Trifluoroacetic acid → HCID 118059798, compound

HRID 632533Notes

Reaction equation

HRID 632533 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].FC(F)(F)C(O)=O.[NH2:22][C:23]1[C:24]([C:28]2[N:32]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[C:35]([Br:40])[CH:34]=3)[C:31](=[O:41])[O:30][N:29]=2)=[N:25][O:26][N:27]=1.[CH2:42]([N:45]([S:53]([N:56]([CH2:60][CH:61]=[CH2:62])[CH2:57][CH:58]=O)(=[O:55])=[O:54])[C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH:43]=[CH2:44].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1>[CH2:42]([N:45]([S:53](=[O:55])(=[O:54])[N:56]([CH2:60][CH:61]=[CH2:62])[CH2:57][CH2:58][NH:22][C:23]1[C:24]([C:28]2[N:32]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[C:35]([Br:40])[CH:34]=3)[C:31](=[O:41])[O:30][N:29]=2)=[N:25][O:26][N:27]=1)[C:46](=[O:52])[O:47][C:48]([CH3:49])([CH3:51])[CH3:50])[CH:43]=[CH2:44]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acid2×HCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 591483883-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-oneHCID 118060319HCID 118060319, compound2×

Product 1

HCID 118059798HCID 118059798, compoundYield 74.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-5 °C

Procedure

To a 50-mL flask was added sodium triacetoxyborohydride (1.06 g, 5.0 mmol, 1.0 equiv.), trifluoroacetic acid (TFA, 2.0 mL, 26 mmol) and tetrahydrofuran (THF, 1.0 mL) at ambient temperature. This mixture was cooled to −5° C. under N2 and stirred at 0-5° C. for 10 min. To this solution was added 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (0.171 g, 5.0 mmol; Step D) and tert-butyl allyl{[allyl(2-oxoethy)amino]sulfonyl}carbamate (0.398 g, 2.5 mmol, 0.5 equiv.) in THF (1.5 mL) drop-wise at 0-5° C. over 5 min. The resulting reaction mixture was stirred under N2 at 0-5° C. At 20 min, 40 min, and 2.5 h time points, a solution of tert-butyl allyl{[allyl(2-oxoethy)amino]sulfonyl}carbamate (0.040 g, 0.125 mmol, 0.25 equiv.) in THF (0.20 mL) was added drop-wise at 0-5° C. At 2.5 h, a solution of sodium triacetoxyborohydride (0.211 g, 1.0 mmol, 0.2 equiv.) in trifluoroacetic acid (TFA, 1.5 mL, 9.5 mmol) was added at 0-5° C. The reaction was warmed to room temperature and stirred overnight. The reaction mixture was then poured into an ice-cold saturated solution of sodium carbonate (50 mL) and extracted with dichloromethane (3×20 mL). The combined dichloromethane extracts were washed with brine, dried over sodium sulfate, and concentrated. The residue was then purified on silica gel (0-75% ethyl acetate/hexane gradient elution) to give the desired product (0.239 g, 74.2%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.07 (m, 1H), 7.71 (m, 1H), 7.58 (t, 1H, J=8.7 Hz), 6.62 (m, 1H), 5.77 (m, 2H), 5.19 (m, 4H), 4.17 (m, 2H), 3.89 (m, 2H), 3.44 (m, 2H), 3.38 (m, 2H), 1.42 (s, 9H); C23H27BrFN7O7S (MW 644.47), LCMS (EI) m/e 544/546 (M+-Boc+H).

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred under N2 at 0-5° C
  3. waitAt 20 min
  4. waitAt 2.5 h
  5. temperatureThe reaction was warmed to room temperature
  6. stirringstirred overnight
  7. extractionextracted with dichloromethane (3×20 mL)
  8. washThe combined dichloromethane extracts were washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customThe residue was then purified on silica gel (0-75% ethyl acetate/hexane gradient elution)

Sources & evidence

ORD record
ord-f85f377997e1491ea314e5c891a02f3e
Source dataset
uspto-grants-2016_04
Patent number
US09321755B2

Reaction notes

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