Nitrogen → 3-(4-chloropyrimidin-2-yl)-5-(2,6-difluorophenyl)-1-tosyl-1H-indole

HRID 1529304Notes

Reaction equation

HRID 1529304 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([S:18]([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH:13]=[C:12]2I.[Cl:29][C:30]1[CH:35]=[CH:34][N:33]=[C:32]([Sn](CCCC)(CCCC)CCCC)[N:31]=1.N#N>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:29][C:30]1[CH:35]=[CH:34][N:33]=[C:32]([C:12]2[C:11]3[C:15](=[CH:16][CH:17]=[C:9]([C:3]4[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=4[F:8])[CH:10]=3)[N:14]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH:13]=2)[N:31]=1

Participants

7

Reactant 3

HCID 947NitrogenHCID 149763044-Chloro-2-(tributylstannyl)pyrimidineHCID 679602665-(2,6-difluorophenyl)-3-iodo-1-tosyl-1H-indole

Product 1

HCID 867097683-(4-chloropyrimidin-2-yl)-5-(2,6-difluorophenyl)-1-tosyl-1H-indoleYield 26%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-(2,6-difluorophenyl)-3-iodo-1-tosyl-1H-indole (2.0 g, 3.92 mmol) and 4-chloro-2-tributylstannanyl-pyrimidine (2.38 g, 5.98 mmol) in DMF (60 mL) was bubbled N2 for 15 min and added CuI (0.898 g, 4.71 mmol) and Pd(PPh3)4 (0.226 g, 0.196 mmol). The reaction mixture was heated at 80° C. for 1 h and cooled to RT. The reaction mixture was quenched with water and precipitate was formed. The resulting precipitate was collected by filtration, washed with water, and dried to yield crude product. Purification by silica gel column chromatography, eluting with 10% EtOAc in hexanes obtained the title compound (0.50 g, 26%). MS (ESI, pos. ion) m/z: 496.0 (M+1).

Workup

  1. temperaturecooled to RT
  2. customThe reaction mixture was quenched with water
  3. customprecipitate was formed
  4. filtrationThe resulting precipitate was collected by filtration
  5. washwashed with water
  6. customdried
  7. customto yield crude product
  8. customPurification by silica gel column chromatography
  9. washeluting with 10% EtOAc in hexanes

Sources & evidence

ORD record
ord-35084e243d854caa8a72d4544b797032
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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