1-Methyl-3-(tributylstannyl)-1H-indazole-6-carbonitrile → (7-(tert-butylcarbamoyl)-2-(6-cyano-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-5-yl)methyl pivalate

HRID 246597Notes

Reaction equation

HRID 246597 reaction equation
[C:1]([O:7][CH2:8][N:9]1[C:13]2=[N:14][CH:15]=[C:16](Br)[N:17]=[C:12]2[C:11]([C:19](=[O:25])[NH:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[CH3:26][N:27]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:36]#[N:37])[CH:34]=2)[C:29]([Sn](CCCC)(CCCC)CCCC)=[N:28]1.CN1C([Sn](CCCC)(CCCC)CCCC)C2C(=CC(C#N)=CC=2)N1>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>[C:1]([O:7][CH2:8][N:9]1[C:13]2=[N:14][CH:15]=[C:16]([C:29]3[C:30]4[C:35](=[CH:34][C:33]([C:36]#[N:37])=[CH:32][CH:31]=4)[N:27]([CH3:26])[N:28]=3)[N:17]=[C:12]2[C:11]([C:19](=[O:25])[NH:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

7

Reactant 3

HCID 712798431-Methyl-3-(tributylstannyl)-1H-indazole-6-carbonitrile2×HCID 712806162-methyl-3-(tributylstannyl)-1H-indazole-6-carbonitrileHCID 86677996(2-bromo-7-(tert-butylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-5-yl)methyl pivalate

Product 1

HCID 71279638(7-(tert-butylcarbamoyl)-2-(6-cyano-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-5-yl)methyl pivalateYield 48.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

In a round-bottomed flask, (2-bromo-7-(tert-butylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-5-yl)methyl pivalate (140 mg, 0.34 mmol) and 1-methyl-3-(tributylstannyl)-1H-indazole-6-carbonitrile (crude, containing some 2-methyl-3-(tributylstannyl)-1H-indazole-6-carbonitrile) was dissolved in DMF (5 mL) under nitrogen. Pd(PPh3)4 (20 mg, 0.017 mmol) and CuI (13 mg, 0.068 mmol) were added and mixture sonicated for 5 min while bubbling nitrogen. The reaction mixture was stirred at 80° C. for 16 hours. After solvent removal, the residue was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (3:1 to 1:1, v/v) to give (7-(tert-butylcarbamoyl)-2-(6-cyano-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-5-yl)methyl pivalate (80 mg, 48.5%). MS: (M+H)+=488.3; 1H NMR (300 MHz, DMSO): δ 9.15 (s, 1H), 8.58-8.53 (m, 3H), 7.83 (s, 1H), 6.31 (s, 2H), 4.25 (s, 3H), 1.52 (s, 9H), 1.10 (s, 9H).

Workup

  1. custommixture sonicated for 5 min
  2. customwhile bubbling nitrogen
  3. customAfter solvent removal
  4. customthe residue was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (3:1 to 1:1

Sources & evidence

ORD record
ord-408c3e76136a460184939f9171debfa4
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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