Potassium Carbonate → 5-(2-cyano-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

HRID 1473286Notes

Reaction equation

HRID 1473286 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([S:12]([N:15](CC1C=CC(OC)=CC=1OC)[C:16]1[S:20][N:19]=[CH:18][N:17]=1)(=[O:14])=[O:13])=[CH:7]2.C(=O)([O-])[O-].[K+].[K+].[C:38]([C:40]1[CH:45]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:43]=[CH:42][C:41]=1B(O)O)#[N:39].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[C:38]([C:40]1[CH:45]=[C:44]([C:46]([F:47])([F:48])[F:49])[CH:43]=[CH:42][C:41]=1[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([S:12]([NH:15][C:16]1[S:20][N:19]=[CH:18][N:17]=1)(=[O:14])=[O:13])=[CH:7]2)#[N:39]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 532165992-Cyano-4-(trifluoromethyl)phenylboronic acid2×HCID 866873455-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide2×

Product 1

HCID 866873445-(2-cyano-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamideYield 1.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A pressure vessel was charged with 5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (Intermediate D) (150 mg, 0.288 mmol), potassium carbonate (199 mg, 1.441 mmol), (2-cyano-4-(trifluoromethyl)phenyl)boronic acid (124 mg, 0.576 mmol), tetrakis(triphenylphosphine)palladium(0) (33.3 mg, 0.029 mmol), dioxane (1922 μl) and water (961 μl). The reaction was heated in a microwave to 100° C. for 60 min. Additional (2-cyano-4-(trifluoromethyl)phenyl)boronic acid (124 mg, 0.576 mmol) and tetrakis(triphenylphosphine)palladium(0) (33.3 mg, 0.029 mmol) were added and the resulting mixture was heated in a microwave at 100° C. for an additional hour. After heating the mixture was allowed to cool to room temperature, the organic layer was separated and the organic layer was concentrated. The resulting product was purified by MPLC (40 g silica gel column, eluting with 0% to 50% EtOAc in heptane) to afford a white solid that was further purified by reverse phase HPLC (Column: Xbridge 19×100 mm, 5 μm, Waters, Milford, Mass., Flow rate: 40 mL/min, Mobile phase: 0.1% NH4OH in ACN and water). The fractions containing product were dried under a vacuum to afford 5-(2-cyano-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (2.1 mg, 0.004 mmol) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.58 (d, J=8.76 Hz, 1H) 7.69-7.74 (m, 1H) 7.75-7.83 (m, 2H) 7.87 (d, J=8.01 Hz, 1H) 8.16-8.24 (m, 2H) 8.34 (d, J=8.34 Hz, 1H) 8.52-8.57 (m, 2H); m/z (ESI) 461.0 (M+H)+.

Workup

  1. temperaturethe resulting mixture was heated in a microwave at 100° C. for an additional hour
  2. temperatureAfter heating the mixture
  3. temperatureto cool to room temperature
  4. customthe organic layer was separated
  5. concentrationthe organic layer was concentrated
  6. customThe resulting product was purified by MPLC (40 g silica gel column, eluting with 0% to 50% EtOAc in heptane)
  7. customto afford a white solid
  8. customthat was further purified by reverse phase HPLC (Column: Xbridge 19×100 mm, 5 μm, Waters, Milford, Mass., Flow rate: 40 mL/min, Mobile phase: 0.1% NH4OH in ACN and water)
  9. additionThe fractions containing product
  10. customwere dried under a vacuum

Sources & evidence

ORD record
ord-6baa9c1aa5b04f2f97638fa02b07eb7d
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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