Potassium Carbonate → 2-(4-trifluoromethylphenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

HRID 1898649ノート

反応式

HRID 1898649 の反応式
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:33])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21](Br)[N:22]=3)[N:17]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2].[F:34][C:35]([F:46])([F:45])[C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.C(=O)([O-])[O-].[K+].[K+].C(=O)(O)[O-].[Na+]>O1CCOCC1.O.[Cl-].[Cl-].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd+2].C(OCC)(=O)C>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:33])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:39]4[CH:40]=[CH:41][C:36]([C:35]([F:46])([F:45])[F:34])=[CH:37][CH:38]=4)[N:22]=3)[N:17]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2]

参加物

9

反応物 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 58438590HCID 58438590、化合物

生成物 1

HCID 673864092-(4-trifluoromethylphenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide収率 66.8%

試薬・触媒・溶媒 4

HCID 178478645Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒2 回HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

In a microwave vial, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (80 mg, 0.15 mmol) was dissolved in 1.5 mL of 1,4-dioxane and 0.35 mL of water. The solution was purged with Ar gas then 4-(trifluoromethyl)phenylboronic acid (31 mg, 0.165 mmol), palladium bis-(diphenylphosphino)ferrocene dichloride, dichloromethane complex (6.1 mg, 0.008 mmol) and potassium carbonate (62 mg, 0.45 mmol) were added. The reaction vessel was sealed and heated in a microwave reactor at 150° C. for 30 min. The reaction was cooled and water and ethyl acetate were added. The mixture was poured into ethyl acetate and sodium bicarbonate solution. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) to give 60 mg (66%) of 2-(4-trifluoromethylphenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide.

後処理

  1. customThe solution was purged with Ar gas
  2. customThe reaction vessel was sealed
  3. temperatureThe reaction was cooled
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted twice more with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. customAfter evaporation
  9. customthe residue was purified by silica gel chromatography (methanol/dichloromethane)

出典と根拠

ORDレコード
ord-4dd442c15e564bcdbd6282e403c0b4d7
出典データセット
uspto-grants-2013_08
特許番号
US08518945B2

反応ノート

読み込み中…