2-Chloro-6-(tributylstannyl)pyrazine → 3-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1529375Notes

Reaction equation

HRID 1529375 reaction equation
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[N:15]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:14]=[C:13]4I)[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1.[Cl:26][C:27]1[CH:32]=[N:31][CH:30]=[C:29]([Sn](CCCC)(CCCC)CCCC)[N:28]=1>CN(C=O)C.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.[Cu]I>[Cl:26][C:27]1[N:28]=[C:29]([C:13]2[C:12]3[C:16](=[CH:17][CH:18]=[C:10]([C:8]4[CH:7]=[N:6][CH:5]=[C:4]([CH:1]5[CH2:3][CH2:2]5)[N:9]=4)[CH:11]=3)[N:15]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:14]=2)[CH:30]=[N:31][CH:32]=1

Participants

6

Reactant 2

HCID 117740572-Chloro-6-(tributylstannyl)pyrazineHCID 679600395-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Product 1

HCID 867097793-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 35.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
105 °C

Procedure

A glass microwave reaction vessel was charged with 5-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (140 mg, 0.31 mmol), 2-chloro-6-(tributylstannyl)pyrazine (190 mg, 0.47 mmol), Pd(PPh3)4 (18 mg, 0.016 mmol) and CuI (6 mg, 0.031 mmol) in DMF (1 mL). Argon was bubbled through the mixture for 5 min. The tube was sealed and the mixture was heated to 105° C. for 2 h. The reaction was diluted with EtOAc and water and filtered through celite. The crude was purified by silica gel chromatography, eluting with a gradient of 0-50% EtOAc in hexanes, to provide 3-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (48 mg, 0.11 mmol, 35% yield) as a light-yellow solid. MS (ESI, pos. ion) m/z: 433.0 (M+1).

Workup

  1. customA glass microwave reaction vessel
  2. customArgon was bubbled through the mixture for 5 min
  3. customThe tube was sealed
  4. additionThe reaction was diluted with EtOAc and water
  5. filtrationfiltered through celite
  6. customThe crude was purified by silica gel chromatography
  7. washeluting with a gradient of 0-50% EtOAc in hexanes

Sources & evidence

ORD record
ord-7be510b86e5248bd92a2b5832f49840a
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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