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

HRID 246644Notes

Reaction equation

HRID 246644 reaction equation
Br[C:2]1[N:7]=[C:6]2[C:8]([C:19]([O:21][CH3:22])=[O:20])=[CH:9][N:10]([CH2:11][O:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[C:5]2=[N:4][CH:3]=1.[Cl:23][C:24]1[CH:32]=[C:31]2[C:27]([C:28]([Sn](CCCC)(CCCC)CCCC)=[N:29][NH:30]2)=[CH:26][CH:25]=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:23][C:24]1[CH:32]=[C:31]2[C:27]([C:28]([C:2]3[N:7]=[C:6]4[C:8]([C:19]([O:21][CH3:22])=[O:20])=[CH:9][N:10]([CH2:11][O:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[C:5]4=[N:4][CH:3]=3)=[N:29][NH:30]2)=[CH:26][CH:25]=1

Participants

6

Reactant 2

HCID 86677991methyl 2-bromo-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylateHCID 1784482296-chloro-3-(tributylstannyl)-1H-indazole

Product 1

HCID 71280196methyl 2-(6-chloro-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylateYield 85.7%

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

A mixture of methyl 2-bromo-5-(pivaloyloxymethyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylate (0.26 g, 0.7 mmol), 6-chloro-3-(tributylstannyl)-1H-indazole (0.31 g, 0.7 mmol), Pd(PPh3)4 (81 mg, 0.07 mmol) and CuI (27 mg, 0.14 mmol) in dry DMF (3 mL) was heated to 90° C. for 3 hours. Product was extracted with ethyl acetate (60 mL), and organic phase washed with water (3×10 mL) and brine (2×10 mL), dried over Na2SO4, filtered and concentrated to afford methyl 2-(6-chloro-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylate (265 mg, crude) as a brown oil. LCMS: (M+H)+=442.

Workup

  1. extractionProduct was extracted with ethyl acetate (60 mL), and organic phase
  2. washwashed with water (3×10 mL) and brine (2×10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-bb723ae048e0440587d99b56e65766bf
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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