Trifluoroacetic acid → HCID 118069745, compound

HRID 632539Notes

Reaction equation

HRID 632539 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:39])[O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)(=[O:28])=[O:27].FC(F)(F)C(O)=O.C([SiH](CC)CC)C>ClCCCl>[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:39])[O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)(=[O:27])=[O:28])=[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 118060399HCID 118060399, compound

Product 1

HCID 118069745HCID 118069745, compoundYield 104.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (68 mg, 0.20 mmol; from Step D) and benzyl {[(2,2-dimethoxyethyl)amino]sulfonyl}carbamate (191 mg, 0.60 mmol, 3.0 equiv.) in 1,2-dichloroethane (3.0 mL) was cooled to 0° C. To this mixture was added trifluoroacetic acid (1.0 mL, 13.0 mmol) and triethylsilane (105 μL, 0.66 mmol, 3.3 equiv.) drop-wise. This reaction mixture was stirred at 0° C. for 2 h. HPLC indicated reaction completion. The reaction mixture was cooled to 0° C. and quenched with saturated sodium bicarbonate to pH ˜8. and the quenched reaction mixture was extracted with EtOAc (3×10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated. The residue was then stirred in a mixture of heptane and diethyl ether overnight. The solids were collected by filtration, washed with heptane and dried in vacuum to give the desired product (125 mg, 99%) as a crude off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 11.31 (s, 1H), 8.05 (m, 1H), 7.87 (m, 1H), 7.68 (m, 1H), 7.56 (m, 1H), 7.32 (m, 5H), 6.54 (m, 1H), 5.07 (s, 2H), 3.29 (m, 2H), 3.09 (m, 2H); C20H17BrFN7O7S (MW 598.36), LCMS m/e 598/600 (M++H).

Workup

  1. customreaction completion
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customquenched with saturated sodium bicarbonate to pH ˜8
  4. customand the quenched reaction mixture
  5. extractionwas extracted with EtOAc (3×10 mL)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. stirringThe residue was then stirred in a mixture of heptane and diethyl ether overnight
  10. filtrationThe solids were collected by filtration
  11. washwashed with heptane
  12. customdried in vacuum

Sources & evidence

ORD record
ord-e242c662bcf44d88b37b6e69b2bf6a58
Source dataset
uspto-grants-2016_04
Patent number
US09321755B2

Reaction notes

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