4-(4-Methoxybenzyloxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidine → 5-bromo-3-(6-((4-methoxybenzyl)oxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1529438Notes

Reaction equation

HRID 1529438 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2I.[CH3:18][O:19][C:20]1[CH:41]=[CH:40][C:23]([CH2:24][O:25][C:26]2[CH:31]=[C:30]([Sn](C)(C)C)[N:29]=[C:28]([S:36]([CH3:39])(=[O:38])=[O:37])[N:27]=2)=[CH:22][CH:21]=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>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[C:30]1[CH:31]=[C:26]([O:25][CH2:24][C:23]2[CH:22]=[CH:21][C:20]([O:19][CH3:18])=[CH:41][CH:40]=2)[N:27]=[C:28]([S:36]([CH3:39])(=[O:38])=[O:37])[N:29]=1

Participants

7

Reactant 2

HCID 679579354-(4-Methoxybenzyloxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidineHCID 679597555-bromo-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Product 1

HCID 679596205-bromo-3-(6-((4-methoxybenzyl)oxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 44%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
90 °C

Procedure

A glass microwave reaction vessel was charged with 5-bromo-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.82 g, 2.015 mmol) and 4-((4-methoxybenzyl)oxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidine (1.013 g, 2.216 mmol) in DMF (5 mL) followed by Pd(PPh3)4 (0.116 g, 0.101 mmol) and CuI (0.017 ml, 0.504 mmol). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 90° C. for 30 min. The mixture was diluted with DCM (5 mL), filtered through a plug of celite and washed with DCM. The filtrate was washed with water (25 mL×3) and the organic layer was dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 0-10% EtOAc in Hexanes) to give 5-bromo-3-(6-((4-methoxybenzyl)oxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (508 mg, 0.886 mmol, 44.0% yield) as a white foam. MS (ESI, pos. ion) m/z: 573/575 (1:1) (M+1); 1H NMR (400 MHz, CDCl3) δ ppm 1.67-1.86 (m, 3 H) 2.06-2.26 (m, 2 H) 2.49-2.64 (m, 1 H) 3.48 (s, 3 H) 3.72-3.80 (m, 1 H) 3.82 (s, 3 H) 3.91-4.01 (m, 1H) 5.52 (s, 2 H) 5.79 (dd, J=8.41, 2.93 Hz, 1 H) 6.93 (m, J=8.80 Hz, 2 H) 7.45 (m, J=8.80 Hz, 2 H) 7.51-7.60 (m, 2 H) 7.70 (s, 1 H) 8.68-8.74 (m, 1 H).

Workup

  1. customA glass microwave reaction vessel
  2. filtrationfiltered through a plug of celite
  3. washwashed with DCM
  4. washThe filtrate was washed with water (25 mL×3)
  5. customthe organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified with silica gel chromatography (eluting with 0-10% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-7353134da79b4cabbda5d4b6238407bc
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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