4-(4-Methoxybenzyloxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidine → 5-(2,6-difluorophenyl)-3-(6-(4-methoxybenzyloxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1529435Notes

Reaction equation

HRID 1529435 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.[CH3:25][O:26][C:27]1[CH:48]=[CH:47][C:30]([CH2:31][O:32][C:33]2[CH:38]=[C:37]([Sn](C)(C)C)[N:36]=[C:35]([S:43]([CH3:46])(=[O:45])=[O:44])[N:34]=2)=[CH:29][CH:28]=1>CN(C=O)C.C(Cl)Cl.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>[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]2[C:37]1[CH:38]=[C:33]([O:32][CH2:31][C:30]2[CH:29]=[CH:28][C:27]([O:26][CH3:25])=[CH:48][CH:47]=2)[N:34]=[C:35]([S:43]([CH3:46])(=[O:45])=[O:44])[N:36]=1

Participants

7

Reactant 2

HCID 679579354-(4-Methoxybenzyloxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidineHCID 679597535-(2,6-difluoro-phenyl)-3-iodo-1-(tetrahydro-pyran-2-yl)-1H-indazole

Product 1

HCID 679598545-(2,6-difluorophenyl)-3-(6-(4-methoxybenzyloxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 88.3%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 5-(2,6-difluorophenyl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (347 mg, 0.788 mmol) and 4-(4-methoxybenzyloxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidine (360 mg, 0.788 mmol) in DMF (3 mL) followed by Pd(PPh3)4 (45.5 mg, 0.039 mmol) and CuI (31 mg, 0.158 mmol). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 30 min. The mixture was diluted with DCM and washed with water, brine, dried with MgSO4, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 10-30% EtOAc in Hexanes) to give 5-(2,6-difluorophenyl)-3-(6-(4-methoxybenzyloxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (422 mg, 0.696 mmol, 88% yield) as a yellow solid. MS (ESI, pos. ion) m/z: 606.5 (M+1).

Workup

  1. customA glass microwave reaction vessel
  2. washwashed with water, brine
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified with silica gel chromatography (eluting with 10-30% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-9decb2724955488cbde88722cc69ebef
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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