HCID 46208543, compound → HCID 46901483, compound

HRID 1879102Notes

Reaction equation

HRID 1879102 reaction equation
[C:1]([C:3]([NH:18][C:19](=[O:31])[C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=1)([CH3:17])[CH2:4][N:5]1[N:9]=[C:8]2[C:10]([Cl:16])=[CH:11][C:12]([Cl:15])=[C:13]([Cl:14])[C:7]2=[N:6]1)#[N:2].[NH4+]=[S:33]>CO>[CH3:17][C:3]([NH:18][C:19](=[O:31])[C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]([F:28])([F:30])[F:29])=[CH:22][CH:21]=1)([C:1](=[S:33])[NH2:2])[CH2:4][N:5]1[N:9]=[C:8]2[C:10]([Cl:16])=[CH:11][C:12]([Cl:15])=[C:13]([Cl:14])[C:7]2=[N:6]1

Participants

3

Reactant 1

HCID 46208543HCID 46208543, compound2×

Product 1

HCID 46901483HCID 46901483, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of N-[1-Cyano-1-methyl-2-(4,5,7-trichloro-2H-benzotriazol-2-yl)-ethyl]-4-trifluoromethoxybenzamide (60 mg, 0.12 mmole, described in U.S. Provisional Application SN: 60/930,485 as compound 1.064) and ammonium sulfide (0.04 mL, 40-48 wt. % in water from Sigma-Aldrich) in methanol (4 mL) was irradiated for 20 minute in a self-tunable CEM microwave Discover synthesizer at 80° C. (initial power 100 Watts) and then cooled using a flow of compressed air, evaporated in vacuo and partitioned between ethyl acetate and water. The aqueous layer was further extracted with ethyl acetate. The organic extracts were combined, washed with brine, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give a residue that that was purified by chromatography (SiO2, heptane/ethyl acetate) to afford the title compound as a solid (30 mg, 47%) along with recovered starting material (22 mg, 37%). MS (ES): M/Z [M+H]=526 and [M−H]=524. 1H NMR: (400 MHz, DMSO-d6): 1.48 (s, 3H), 5.59 (d, J=13.3 Hz, 1H), 5.70 (, J=13.3 Hz, 1H), 7.44 (d, J=8.0 Hz, 2H), 7.88 (s, 1H), 7.93 (d, J=8.8 Hz, 2H), 8.16 (s, 1H), 9.34 (s, 1H) and 9.83 (s, 1H). 19F NMR (376 MHz, DMSO-d6): −57.2 (s, 3F).

Workup

  1. temperaturethen cooled
  2. customevaporated in vacuo
  3. custompartitioned between ethyl acetate and water
  4. extractionThe aqueous layer was further extracted with ethyl acetate
  5. washwashed with brine
  6. washwashed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give a residue that
  11. customthat was purified by chromatography (SiO2, heptane/ethyl acetate)

Sources & evidence

ORD record
ord-80bb1c8d2ad246f58e3ca91dbc6a3ab2
Source dataset
uspto-grants-2012_11
Patent number
US08314146B2

Reaction notes

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