Trifluoroacetic acid → HCID 86710171, compound

HRID 705393Notes

Reaction equation

HRID 705393 reaction equation
[CH:1]1([C:4]2[C:5]([N:25]([CH2:30][CH2:31][CH2:32][C:33]([NH:35][NH:36]C(OC(C)(C)C)=O)=[O:34])[S:26]([CH3:29])(=[O:28])=[O:27])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9]([C:19]4[NH:20][CH:21]=[CH:22][N:23]=4)[C:8]=3[CH:24]=2)[CH2:3][CH2:2]1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH:1]1([C:4]2[C:5]([N:25]([CH2:30][CH2:31][CH2:32][C:33]([NH:35][NH2:36])=[O:34])[S:26]([CH3:29])(=[O:28])=[O:27])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9]([C:19]4[NH:20][CH:21]=[CH:22][N:23]=4)[C:8]=3[CH:24]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131733692HCID 131733692, compound

Product 1

HCID 86710171HCID 86710171, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of tert-butyl 2-(4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(1H-imidazol-2-yl)benzofuran-6-yl)methylsulfonamido)butanoyl)hydrazinecarboxylate (40 mg, 0.065 mmol) in anhydrous CH2Cl2 (0.5 mL) under nitrogen was cooled to 0° C., and treated with trifluoroacetic acid (0.5 mL). The reaction was stirred at 25° C. for 1 hour. The mixture was concentrated by rotary evaporation, and the residue was diluted with ethyl acetate (50 mL), and washed with 5% aqueous NaHCO3 (2×10 mL) and brine (10 mL). The organic phase was dried over anhydrous MgSO4, filtered, and concentrated by rotary evaporation. The crude material was purified by SiO2 flash chromatography (Alltech Extract-Clean™ column, 5 g bed) eluting with a step gradient of 5% methanol/CH2Cl2 to 10% methanol/CH2Cl2 to afford the title compound as a white solid (16 mg, 0.031 mmol, 48%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.50-0.64 (m, 1H), 0.80-0.90 (m, 1H), 0.92-1.08 (m, 2H), 1.59-1.75 (m, 2H), 2.02-2.17 (m, 2H), 2.34-2.42 (m, 1H), 3.15 (s, 3H), 3.55-3.77 (m, 2H), 4.12 (d, J=4.12 Hz, 2H), 7.08 (s, 1H), 7.18 (s, 1H), 7.28-7.43 (m, 3H), 7.85 (s, 1H), 8.02 (dd, J=9.00, 5.53 Hz, 2H), 8.93 (t, J=3.36 Hz, 1H), 12.41 (s, 1H); MS (ESI+) m/z 512 (M+H)+, 1023 (2M+H)+.

Workup

  1. concentrationThe mixture was concentrated by rotary evaporation
  2. additionthe residue was diluted with ethyl acetate (50 mL)
  3. washwashed with 5% aqueous NaHCO3 (2×10 mL) and brine (10 mL)
  4. dry with materialThe organic phase was dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. customThe crude material was purified by SiO2 flash chromatography (Alltech Extract-Clean™ column, 5 g bed)
  8. washeluting with a step gradient of 5% methanol/CH2Cl2 to 10% methanol/CH2Cl2

Sources & evidence

ORD record
ord-f3c56aa11e824af986e49efa220df0d2
Source dataset
uspto-grants-2015_11
Patent number
US09173887B2

Reaction notes

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