Potassium Phosphate, Tribasic → 1-(2-{5-Fluoro-4-[7-(2-fluoro-5-(fluoromethyl)pyridin-4-yl)benzo[b]thiophen-2-yl]pyrimidin-2-ylamino}ethyl)imidazolidin-2-one

HRID 422115ノート

反応式

HRID 422115 の反応式
[F:1][C:2]1[C:3]([C:17]2[S:21][C:20]3[C:22](B4OC(C)(C)C(C)(C)O4)=[CH:23][CH:24]=[CH:25][C:19]=3[CH:18]=2)=[N:4][C:5]([NH:8][CH2:9][CH2:10][N:11]2[CH2:15][CH2:14][NH:13][C:12]2=[O:16])=[N:6][CH:7]=1.[F:35][C:36]1[CH:41]=[C:40](I)[C:39]([CH2:43][F:44])=[CH:38][N:37]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C(Cl)(Cl)Cl.C(O)(C)C>[F:1][C:2]1[C:3]([C:17]2[S:21][C:20]3[C:22]([C:40]4[C:39]([CH2:43][F:44])=[CH:38][N:37]=[C:36]([F:35])[CH:41]=4)=[CH:23][CH:24]=[CH:25][C:19]=3[CH:18]=2)=[N:4][C:5]([NH:8][CH2:9][CH2:10][N:11]2[CH2:15][CH2:14][NH:13][C:12]2=[O:16])=[N:6][CH:7]=1

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 666734811-(2-{5-Fluoro-4-[7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophen-2-yl]-pyrimidin-2-ylamino}-ethyl)-imidazolidin-2-oneHCID 66674186HCID 66674186、化合物

生成物 1

HCID 249363441-(2-{5-Fluoro-4-[7-(2-fluoro-5-(fluoromethyl)pyridin-4-yl)benzo[b]thiophen-2-yl]pyrimidin-2-ylamino}ethyl)imidazolidin-2-one収率 58.2%

試薬・触媒・溶媒 2

HCID 312751,4-Dioxane溶媒HCID 21906603Chloroform isopropyl alcohol溶媒

反応条件

温度
100 °C

実験手順

Combine 1-(2-{5-fluoro-4-[7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophen-2-yl]-pyrimidin-2-ylamino}-ethyl)-imidazolidin-2-one (120 mg, 248.26 μmol), 2-fluoro-5-fluoromethyl-4-iodo-pyridine (100 mg, 392.15 μmol) tris(dibenzylideneacetone)dipalladium (0) (11.37 mg, 12.41 μmol) tricyclohexylphosphine (2.09 mg, 7.45 μmol), potassium phosphate (105.39 mg, 496.51 μmol) in 5 mL of dioxane in a sealed pressure tube. Heat the mixture at 100° C. for 3 hours in the oil bath. LC-MS shows a peak at 485. Cool the reaction mixture down to room temperature and dilute it with chloroform-isopropyl alcohol (3/1). Wash the organic solution with saturated aqueous sodium chloride, dry it over sodium sulfate and concentrate it to crude. Purify the crude by flash chromatography (10% methanol in dichloromethane) to give the target product (70 mg, 58.2%). MS (ES) m/z 485 [M+1]+.

後処理

  1. temperatureCool the reaction mixture down to room temperature
  2. washWash the organic solution with saturated aqueous sodium chloride
  3. dry with materialdry it over sodium sulfate
  4. concentrationconcentrate it to crude
  5. customPurify the crude by flash chromatography (10% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-9dd6529e98664fe28c13ba848cdf5705
出典データセット
uspto-grants-2012_01
特許番号
US08101628B2

反応ノート

読み込み中…