Potassium Phosphate, Tribasic → N-(2,4-dimethoxybenzyl)-1-methyl-3-(3-(pyridin-4-yl)-5-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

HRID 1524410Notes

Reaction equation

HRID 1524410 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:12]2[C:20]3[C:15](=[CH:16][C:17]([S:21]([N:24]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][C:32]=4[O:39][CH3:40])[C:25]4[S:29][N:28]=[CH:27][N:26]=4)(=[O:23])=[O:22])=[CH:18][CH:19]=3)[N:14]([CH3:41])[CH:13]=2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[N:42]1[CH:47]=[CH:46][C:45](B(O)O)=[CH:44][CH:43]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[CH3:40][O:39][C:32]1[CH:33]=[C:34]([O:37][CH3:38])[CH:35]=[CH:36][C:31]=1[CH2:30][N:24]([C:25]1[S:29][N:28]=[CH:27][N:26]=1)[S:21]([C:17]1[CH:16]=[C:15]2[C:20]([C:12]([C:4]3[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=[C:2]([C:45]4[CH:46]=[CH:47][N:42]=[CH:43][CH:44]=4)[CH:3]=3)=[CH:13][N:14]2[CH3:41])=[CH:19][CH:18]=1)(=[O:23])=[O:22]

Participants

4

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acidHCID 90388211HCID 90388211, compound

Product 1

HCID 71259417N-(2,4-dimethoxybenzyl)-1-methyl-3-(3-(pyridin-4-yl)-5-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

Procedure

A microwave vial was charged with 3-(3-bromo-5-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (0.050 g, 0.075 mmol), pyridin-4-ylboronic acid (0.018 g, 0.150 mmol), potassium phosphate (0.056 g, 0.262 mmol), and Pd(AmPhos)2Cl2 (5.30 mg, 7.49 μmol). The vial was flushed with Ar, then dioxane (0.375 ml) and water (0.125 ml) were added in sequence. The vial was sealed and microwaved at 100° C. for 30 minutes. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with brine, dried with sodium sulfate, filtered and concentrated. The material was purified via column chromatography (silica gel, gradient elution 0 to 100% EtOAc/Heptane) to afford N-(2,4-dimethoxybenzyl)-1-methyl-3-(3-(pyridin-4-yl)-5-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide as a yellow solid. m/z (ESI) 666.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar
  2. additiondioxane (0.375 ml) and water (0.125 ml) were added in sequence
  3. customThe vial was sealed
  4. custommicrowaved at 100° C. for 30 minutes
  5. additionThe reaction was diluted with ethyl acetate
  6. washwashed with water
  7. extractionThe aqueous layer was extracted with ethyl acetate
  8. washthe combined organic layers were washed with brine
  9. dry with materialdried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe material was purified via column chromatography (silica gel, gradient elution 0 to 100% EtOAc/Heptane)

Sources & evidence

ORD record
ord-f0c64bbc74484dc693fc9da613dfd9bd
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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