Dimethylformamide → 5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide

HRID 246562Notes

Reaction equation

Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8](COCC[Si](C)(C)C)[C:5]2=[N:6][CH:7]=1.ClC1C=C2C(C([Sn](CCCC)(CCCC)CCCC)=NN2C)=CC=1.CN(C=[O:54])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>[OH:54][CH2:17][C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[CH:2][N:3]=2)[NH:8][CH:9]=1)=[O:12])([CH3:15])[CH3:16]

Participants

Conditions

Temperature: 90 °C

Procedure

2-Bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (90 mg, 0.203 mmol) and 6-chloro-1-methyl-3-(tributylstannyl)-1H-indazole (0.148 g, 0.228 mmol) were dissolved in DMF (3 mL). The reaction mixture was evacuated and filled with nitrogen then copper(I) iodide (9 mg, 0.081 mmol) and tetrakis(triphenylphosphine)palladium (0) (46 mg, 0.046 mmol) were added. The reaction mixture was heated at 90° C. for 2 h then partitioned between ethyl acetate and water. The organic phase was washed with brine then dried over magnesium sulfate. The crude material was purified by chromatography using 25% ethyl acetate/hexane to obtain 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-trimethyl-silanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide (40 mg, 37%).

Workup

customThe reaction mixture was evacuated
additionfilled with nitrogen
customthen partitioned between ethyl acetate and water
washThe organic phase was washed with brine
dry with materialthen dried over magnesium sulfate
customThe crude material was purified by chromatography

Sources & evidence

ORD record: ord-3ed928d963664bd997d27383d055c715
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658646B2

Reaction notes

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