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 422115Notes

Reaction equation

HRID 422115 reaction equation
[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

Participants

6

Reactant 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, compound

Product 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-oneYield 58.2%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Conditions

Temperature
100 °C

Procedure

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]+.

Workup

  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)

Sources & evidence

ORD record
ord-9dd6529e98664fe28c13ba848cdf5705
Source dataset
uspto-grants-2012_01
Patent number
US08101628B2

Reaction notes

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