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

HRID 1524392ノート

反応式

HRID 1524392 の反応式
[CH3:1][O:2][C:3]1[CH:37]=[C:36]([O:38][CH3:39])[CH:35]=[CH:34][C:4]=1[CH2:5][N:6]([C:29]1[S:33][N:32]=[CH:31][N:30]=1)[S:7]([C:10]1[CH:18]=[C:17]2[C:13]([C:14](B3OC(C)(C)C(C)(C)O3)=[CH:15][N:16]2[CH3:19])=[CH:12][CH:11]=1)(=[O:9])=[O:8].[Br:40][C:41]1[CH:46]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:44]=[CH:43][C:42]=1I.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Br:40][C:41]1[CH:46]=[C:45]([C:47]([F:48])([F:49])[F:50])[CH:44]=[CH:43][C:42]=1[C:14]1[C:13]2[C:17](=[CH:18][C:10]([S:7]([N:6]([CH2:5][C:4]3[CH:34]=[CH:35][C:36]([O:38][CH3:39])=[CH:37][C:3]=3[O:2][CH3:1])[C:29]3[S:33][N:32]=[CH:31][N:30]=3)(=[O:8])=[O:9])=[CH:11][CH:12]=2)[N:16]([CH3:19])[CH:15]=1

参加物

5

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 162440892-Bromo-1-iodo-4-(trifluoromethyl)benzeneHCID 71259251N-(2,4-dimethoxybenzyl)-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

生成物 1

HCID 712595893-(2-bromo-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide収率 43.6%

試薬・触媒・溶媒 1

HCID 178418807HCID 178418807、化合物触媒

反応条件

温度
60 °C

実験手順

A vial was charged with N-(2,4-dimethoxybenzyl)-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (0.500 g, 0.876 mmol), 2-bromo-1-iodo-4-(trifluoromethyl)benzene (0.769 g, 2.191 mmol), potassium phosphate (0.651 g, 3.07 mmol), and PdCl2(dppf)-CH2Cl2 (0.072 g, 0.088 mmol). DMF (5.84 ml), and the vial was flushed with argon, sealed, and stirred at 60° C. for two hours. 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:Hexanes) to afford 3-(2-bromo-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (0.255 g, 0.382 mmol, 43.6% yield) as an off-white solid. m/z (ESI) 667.0 (M+H)+.

後処理

  1. customDMF (5.84 ml), and the vial was flushed with argon
  2. customsealed
  3. additionThe reaction was diluted with ethyl acetate
  4. washwashed with water
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe material was purified via column chromatography (silica gel, gradient elution 0 to 100% EtOAc:Hexanes)

出典と根拠

ORDレコード
ord-f623fb13689c4994af7b17d44d348eae
出典データセット
uspto-grants-2015_07
特許番号
US09079902B2

反応ノート

読み込み中…