6-fluoro-1-methyl-3-(tributylstannyl)-1H-indazole → methyl 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate

HRID 246569Notes

Reaction equation

HRID 246569 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([Sn](CCCC)(CCCC)CCCC)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.Br[C:26]1[N:27]=[C:28]2[C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][N:32]([CH2:39][O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C:29]2=[N:30][CH:31]=1>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>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:26]3[N:27]=[C:28]4[C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][N:32]([CH2:39][O:40][C:41](=[O:46])[C:42]([CH3:44])([CH3:43])[CH3:45])[C:29]4=[N:30][CH:31]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 712803076-fluoro-1-methyl-3-(tributylstannyl)-1H-indazoleHCID 86677991methyl 2-bromo-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate

Product 1

HCID 71280132methyl 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylateYield 85.2%

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 stirred solution of 6-fluoro-1-methyl-3-(tributylstannyl)-1H-indazole (0.51 g, 0.616 mmol), methyl 2-bromo-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate (0.18 g, 0.486 mmol) in 6 mL of DMF were added CuI (0.04 g, 0.21 mmol) and Pd(PPh3)4 (0.057 g, 0.045 mmol) in one portion under nitrogen at room temperature. Then the reaction mixture was degassed by bubbling nitrogen for 10 minutes and stirred at 90° C. under nitrogen for 16 hours. The solvent was evaporated at 70° C. under reduced pressure and the residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with a mixture of ethyl acetate and petroleum ether (1:1, v/v) to give methyl 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate (0.182 g, 85.2%) as a yellow solid. LCMS: (M+H)+=440; 1H NMR (300 MHz, DMSO): δ 9.13 (s, 1H), 8.83-8.78 (m, 1H), 8.70 (s, 1H), 7.63 (dd, 1H, J1=9.6 Hz, J2=2.1 Hz), 7.23 (dt, 1H, J1=9.3 Hz, J2=2.1 Hz), 6.30 (s, 2H), 4.13 (s, 3H), 3.92 (s, 3H), 1.08 (s, 9H).

Workup

  1. customThen the reaction mixture was degassed
  2. customby bubbling nitrogen for 10 minutes
  3. customThe solvent was evaporated at 70° C. under reduced pressure
  4. customthe residue was purified by column chromatography (silica gel, 200-300 mesh
  5. washeluting with a mixture of ethyl acetate and petroleum ether (1:1

Sources & evidence

ORD record
ord-ad76c405be7d4c6bb43327b3201c117b
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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