Potassium Phosphate, Tribasic → methyl 3-(4-isopropylpyrimidin-2-yl)-1-tosyl-1H-indole-5-carboxylate

HRID 634205ノート

反応式

HRID 634205 の反応式
CC1(C)C(C)(C)OB([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([O:20][CH3:21])=[O:19])[CH:16]=3)[N:11]([S:22]([C:25]3[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=3)(=[O:24])=[O:23])[CH:10]=2)O1.Cl[C:34]1[N:39]=[C:38]([CH:40]([CH3:42])[CH3:41])[CH:37]=[CH:36][N:35]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:40]([C:38]1[CH:37]=[CH:36][N:35]=[C:34]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([O:20][CH3:21])=[O:19])[CH:16]=3)[N:11]([S:22]([C:25]3[CH:26]=[CH:27][C:28]([CH3:29])=[CH:30][CH:31]=3)(=[O:23])=[O:24])[CH:10]=2)[N:39]=1)([CH3:42])[CH3:41]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 249019162-Chloro-4-isopropylpyrimidineHCID 68328028methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole-5-carboxylate

生成物 1

HCID 68327948methyl 3-(4-isopropylpyrimidin-2-yl)-1-tosyl-1H-indole-5-carboxylate収率 75.1%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A brown mixture of methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole-5-carboxylate (1.85 g, 4.06 mmol), 2-chloro-4-isopropylpyrimidine (0.700 g, 4.47 mmol) [CombiPhos Catalyst Inc.], potassium phosphate (2.59 g, 12.19 mmol), Pd2(dba)3 (0.15 g, 0.16 mmol), and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (X-Phos) (0.15 g, 0.32 mmol) in dioxane (15 mL) and H2O (3.00 mL) was purged with argon then heated in an oil bath at 100° C. for 3 h. The reaction was cooled to RT, diluted with EtOAc (100 mL), washed with NaOH (5 mL of 0.5 N) followed by brine (5 mL). The organic solution was dried and concentrated. Chromatographic purification of the brown residue (20-80% EtOAc/Hex) furnished methyl 3-(4-isopropylpyrimidin-2-yl)-1-tosyl-1H-indole-5-carboxylate (1.37 g, 75%) as a light-yellow solid. This material was used in next step without further purification. MS (ESI, pos. ion) m/z: 450.0 (M+1).

後処理

  1. customwas purged with argon
  2. temperatureThe reaction was cooled to RT
  3. additiondiluted with EtOAc (100 mL)
  4. washwashed with NaOH (5 mL of 0.5 N)
  5. customThe organic solution was dried
  6. concentrationconcentrated
  7. customChromatographic purification of the brown residue (20-80% EtOAc/Hex)

出典と根拠

ORDレコード
ord-8534abe0469247d18d77a4e31587541a
出典データセット
uspto-grants-2016_04
特許番号
US09321756B2

反応ノート

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