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

HRID 246606Notes

Reaction equation

HRID 246606 reaction equation
[C:1]([O:7][CH2:8][N:9]1[C:17]2[C:12](=[N:13][C:14](Br)=[CH:15][N:16]=2)[C:11]([C:19](=[O:33])[NH:20][C:21]([CH3:32])([CH3:31])[CH2:22][O:23][Si](C(C)(C)C)(C)C)=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[CH3:34][N:35]1[C:43]2[C:38](=[CH:39][CH:40]=[C:41]([C:44]#[N:45])[CH:42]=2)[C:37]([Sn](CCCC)(CCCC)CCCC)=[N:36]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>[C:1]([O:7][CH2:8][N:9]1[C:17]2=[N:16][CH:15]=[C:14]([C:37]3[C:38]4[C:43](=[CH:42][C:41]([C:44]#[N:45])=[CH:40][CH:39]=4)[N:35]([CH3:34])[N:36]=3)[N:13]=[C:12]2[C:11]([C:19](=[O:33])[NH:20][C:21]([CH3:31])([CH3:32])[CH2:22][OH:23])=[CH:10]1)(=[O:6])[C:2]([CH3:3])([CH3:5])[CH3:4]

Participants

6

Reactant 2

HCID 712798431-Methyl-3-(tributylstannyl)-1H-indazole-6-carbonitrile2×HCID 86677999(2-bromo-7-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-ylcarbamoyl)-5H-pyrrolo[3,2-b]pyrazin-5-yl)methyl pivalate

Product 1

HCID 71280709(2-(6-cyano-1-methyl-1H-indazol-3-yl)-7-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-5-yl)methyl pivalateYield 16%

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-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-ylcarbamoyl)-5H-pyrrolo[3,2-b]pyrazin-5-yl)methyl pivalate (305 mg, 0.565 mmol) and a crude mixture of 1-methyl-3-(tributylstannyl)-1H-indazole-6-carbonitrile and 1-methyl-3-(tributylstannyl)-1H-indazole-6-carbonitrile were dissolved in DMF (5 mL) under nitrogen. Pd (PPh3)4 (32 mg, 0.028 mmol) and CuI (21 mg, 0.113 mmol) were added and mixture was sonicated for 5 minutes while bubbling nitrogen. The reaction mixture was stirred at 80° C. for 16 hours. The concentrated mixture was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (1:1, v/v) to give (2-(6-cyano-1-methyl-1H-indazol-3-yl)-7-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-5-yl)methyl pivalate (45 mg, 16%). MS: (M+H)+=504.

Workup

  1. custommixture was sonicated for 5 minutes
  2. customwhile bubbling nitrogen
  3. customThe concentrated mixture was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (1:1

Sources & evidence

ORD record
ord-74bbfb115ffb45158dae0ae5b82ed757
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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