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

HRID 1473320Notes

Reaction equation

HRID 1473320 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12]1[C:21]2[C:16](=[CH:17][C:18]([S:22]([N:25]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=3)[C:26]3[S:30][N:29]=[CH:28][N:27]=3)(=[O:24])=[O:23])=[CH:19][CH:20]=2)[CH:15]=[CH:14][N:13]=1.C(=O)([O-])[O-].[K+].[K+].[N:46]1[CH:51]=[CH:50][C:49](B(O)O)=[CH:48][CH:47]=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>[CH3:39][O:38][C:35]1[CH:36]=[CH:37][C:32]([CH2:31][N:25]([C:26]2[S:30][N:29]=[CH:28][N:27]=2)[S:22]([C:18]2[CH:17]=[C:16]3[C:21](=[CH:20][CH:19]=2)[C:12]([C:3]2[CH:4]=[CH:5][C:6]([C:8]([F:9])([F:10])[F:11])=[CH:7][C:2]=2[C:49]2[CH:50]=[CH:51][N:46]=[CH:47][CH:48]=2)=[N:13][CH:14]=[CH:15]3)(=[O:24])=[O:23])=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2734379(Pyridin-4-yl)boronic acidHCID 866873731-(2-bromo-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide

Product 1

HCID 86687374N-(4-methoxybenzyl)-1-(2-(pyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamideYield 100.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with 1-(2-bromo-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide (100 mg, 0.157 mmol), potassium carbonate (109 mg, 0.787 mmol), 4-pyridineboronic acid (77 mg, 0.629 mmol), tetrakis(triphenylphosphine)palladium(0) (18.18 mg, 0.016 mmol), dioxane (1049 μl) and water (525 μl). The vial was purged with argon, sealed and heated in a microwave at 100° C. for 35 min. The reaction was cooled to room temperature, diluted with 60 mL of EtOAc, dried over MgSO4, filtered and concentrated. The material was absorbed onto a plug of silica gel and purified by chromatography through a silica gel column (40 g), eluting with a gradient of 0% to 100% (90:10 MeOH:DCM) in DCM, to provide a yellow glass, N-(4-methoxybenzyl)-1-(2-(pyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide (100 mg, 0.158 mmol). This material was carried on to the next step. MS (ESI): 634.0 [M+H]+.

Workup

  1. customThe vial was purged with argon
  2. customsealed
  3. temperatureThe reaction was cooled to room temperature
  4. additiondiluted with 60 mL of EtOAc
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was absorbed onto a plug of silica gel
  9. custompurified by chromatography through a silica gel column (40 g)
  10. washeluting with a gradient of 0% to 100% (90:10 MeOH:DCM) in DCM

Sources & evidence

ORD record
ord-e2d1329b94884a99a96ddfce0e1f1301
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…