Nitrogen → 3-(2-chloropyrimidin-4-yl)-5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1529289Notes

Reaction equation

HRID 1529289 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]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[N:13]=[C:12]2I.[Cl:25][C:26]1[N:31]=[C:30]([Sn](CCCC)(CCCC)CCCC)[CH:29]=[CH:28][N:27]=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:25][C:26]1[N:31]=[C:30]([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]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[N:13]=2)[CH:29]=[CH:28][N:27]=1

Participants

7

Reactant 3

HCID 947NitrogenHCID 468399532-Chloro-4-(tributylstannyl)pyrimidineHCID 679597535-(2,6-difluoro-phenyl)-3-iodo-1-(tetrahydro-pyran-2-yl)-1H-indazole

Product 1

HCID 867097653-(2-chloropyrimidin-4-yl)-5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 52.1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

To a solution of 5-(2,6-difluorophenyl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole 14 (0.2 g, 0.45 mmol) and 2-Chloro-4-tributylstannanyl-pyrimidine 20a (0.27 g, 0.68 mmol) in DMF was bubbled N2 for 15 min and added CuI (0.052 g, 0.54 mmol) and Pd(PPh3)4 (0.1 g, 0.025 mmol). The reaction mixture was heated at 90° C. for 2 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 5-10% EtOAc and hexanes to obtain the title compound (0.1 g, 38%). MS (ESI, pos. ion) m/z: 427.0 (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 5-10% EtOAc and hexanes

Sources & evidence

ORD record
ord-752b81ea888846b2bdf1d20be594d5a4
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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