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 422115노트

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HRID 422115 반응식
[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

참가 물질

6

반응물 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, 화합물

생성물 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-one수율 58.2%

시약·촉매·용매 2

HCID 312751,4-Dioxane용매HCID 21906603Chloroform isopropyl alcohol용매

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온도
100 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-9dd6529e98664fe28c13ba848cdf5705
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101628B2

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