Potassium Carbonate → 1-(2-chloro-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide

HRID 1473323Notes

Reaction equation

HRID 1473323 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].Cl[C:22]1[C:31]2[C:26](=[CH:27][C:28]([S:32]([N:35](CC3C=CC(OC)=CC=3OC)[C:36]3[S:40][N:39]=[CH:38][N:37]=3)(=[O:34])=[O:33])=[CH:29][CH:30]=2)[CH:25]=[CH:24][N:23]=1.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>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:22]1[C:31]2[C:26](=[CH:27][C:28]([S:32]([NH:35][C:36]3[S:40][N:39]=[CH:38][N:37]=3)(=[O:34])=[O:33])=[CH:29][CH:30]=2)[CH:25]=[CH:24][N:23]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2783251[2-Chloro-4-(trifluoromethyl)phenyl]boronic acidHCID 866873751-chloro-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide

Product 1

HCID 715863251-(2-chloro-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamideYield 22.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A pressure vessel was charged with (2-chloro-4-(trifluoromethyl)phenyl)boronic acid (56.5 mg, 0.252 mmol), potassium carbonate (145 mg, 1.048 mmol), 1-chloro-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide (100 mg, 0.210 mmol), tetrakis(triphenylphosphine)palladium(0) (24.23 mg, 0.021 mmol), dioxane (1398 μl) and water (699 μl). The reaction vessel was swept with nitrogen, sealed with a cap and then heated in a microwave at 100° C. for 30 minutes. The mixture was cooled to room temperature. The organic layer was separated by pipet and then purified by reverse phase HPLC (Column: Gemini 150×30 mm, 5 μm, Phenomenex, Torrance, Calif., Flow rate: 40 mL/min, Mobile phase: 0.1% TFA in ACN and water). The fractions containing pure product were dried under a vacuum to provide 1-(2-chloro-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide (22 mg, 0.047 mmol) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 3.57 (br. s., 1H) 3.63-3.80 (m, 1H) 7.70 (d, J=8.82 Hz, 1H) 7.79 (d, J=7.90 Hz, 1H) 7.86-7.96 (m, 1H) 8.12 (s, 1H) 8.25 (d, J=5.61 Hz, 1H) 8.47 (s, 1H) 8.65 (d, J=1.49 Hz, 1H) 8.77 (d, J=5.73 Hz, 1H); m/z (ESI) 471.0 (M+H)+.

Workup

  1. customsealed with
  2. customa cap
  3. temperatureThe mixture was cooled to room temperature
  4. customThe organic layer was separated by pipet
  5. custompurified by reverse phase HPLC (Column: Gemini 150×30 mm, 5 μm, Phenomenex, Torrance, Calif., Flow rate: 40 mL/min, Mobile phase: 0.1% TFA in ACN and water)
  6. additionThe fractions containing pure product
  7. customwere dried under a vacuum

Sources & evidence

ORD record
ord-2081a87a924c450eb1c6b68909f3c649
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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