Trifluoroacetic acid → HCID 118069695, compound

HRID 632541Notes

Reaction equation

HRID 632541 reaction equation
[NH2:1][C:2]1[C:3]([C:7]2[N:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14]([Br:19])[CH:13]=3)[C:10](=[O:20])[O:9][N:8]=2)=[N:4][O:5][N:6]=1.CO[CH:23](OC)[CH2:24][NH:25][S:26]([NH:29][C:30](=[O:37])[O:31][CH2:32][C:33]([Cl:36])([Cl:35])[Cl:34])(=[O:28])=[O:27].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[Br:19][C:14]1[CH:13]=[C:12]([N:11]2[C:10](=[O:20])[O:9][N:8]=[C:7]2[C:3]2[C:2]([NH:1][CH2:23][CH2:24][NH:25][S:26]([NH:29][C:30](=[O:37])[O:31][CH2:32][C:33]([Cl:36])([Cl:34])[Cl:35])(=[O:28])=[O:27])=[N:6][O:5][N:4]=2)[CH:17]=[CH:16][C:15]=1[F:18]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 591483883-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-oneHCID 118059637HCID 118059637, compound

Product 1

HCID 118069695HCID 118069695, compoundYield 90.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (5, 0.680 g, 1.99 mmol) and 2,2,2-trichloroethyl {[(2,2-dimethoxyethyl)amino]sulfonyl}carbamate (17d, 2.22 g, 6.17 mmol, 3.1 equiv.) in dichloromethane (DCM, 6.0 mL) was stirred at room temperature. To this mixture was added triethylsilane (1.27 mL, 7.95 mmol, 4.0 equiv.) and a solution of trifluoroacetic acid (TFA, 3.0 mL, 39.0 mmol) in dichloromethane (DCM, 2.0 mL) while maintaining the reaction temperature below 30° C. The reaction mixture became homogenous after 5 min with agitation at room temperature and was stirred at room temperature for 1 h. HPLC indicated reaction completion. The reaction was filtered and the precipitate was suspended in a mixture of dichloromethane and heptane (ratio of dichloromethane to heptane was 1 to 9 by volume). The suspension was stirred at room temperature overnight. The precipitate was collected by filtration and washed with 10% dichloromethane in heptane and dried in vacuum to give the desired product (1.15 g, 90.4%) as an off-white solid, which was used in the subsequent reaction without further purification. 1H NMR (300 MHz, DMSO-d6) δ 11.85 (s, 1H), 8.07 (m, 2H), 7.70 (m, 1H), 7.57 (t, 1H, J=8.7 Hz), 6.56 (m, 1H), 4.88 (m, 2H), 3.37 (m, 2H), 3.16 (m, 2H); C15H12BrCl3FN7O7S (MW 639.62), LCMS (EI) m/e 638/640/642 (M++H).

Workup

  1. stirringwas stirred at room temperature for 1 h
  2. customreaction completion
  3. filtrationThe reaction was filtered
  4. additionthe precipitate was suspended in a mixture of dichloromethane and heptane (ratio of dichloromethane to heptane was 1 to 9 by volume)
  5. stirringThe suspension was stirred at room temperature overnight
  6. filtrationThe precipitate was collected by filtration
  7. washwashed with 10% dichloromethane in heptane
  8. customdried in vacuum

Sources & evidence

ORD record
ord-5f2482b1749b47a0bfa0c18157258120
Source dataset
uspto-grants-2016_04
Patent number
US09321755B2

Reaction notes

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