Methyl iodide → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-methoxy-1-methyl-ethyl)-amide

HRID 246149Notes

Reaction equation

HRID 246149 reaction equation
[OH:1][CH2:2][C@H:3]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[N:10]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[CH:9]=1)=[O:7])[CH3:4].[CH3:36]I>[Ag]=O.CC#N>[CH3:36][O:1][CH2:2][C@H:3]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[N:10]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:34])([CH3:33])[CH3:35])[CH:9]=1)=[O:7])[CH3:4]

Participants

5

Reactant 2

HCID 6328Methyl iodideHCID 712860912-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1-methyl-ethyl)-amide

Product 1

HCID 712860582-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-methoxy-1-methyl-ethyl)-amideYield 45%

Reagents, catalysts & solvents 2

HCID 92152Silver(II) oxideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

In a 25 mL round-bottomed flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1-methyl-ethyl)-amide (70 mg, 0.136 mmol), silver oxide (51 mg, 0.22 mmol) and methyl iodide (100 μl, 1.6 mmol) were combined with MeCN to give a black suspension. The round bottom flask was wrapped in foil to exclude light. The system was placed in a sand bath and heated to 40° C. with stirring. The temperature was maintained for 2 days. Upon cooling, the reaction mixture was filtered through a pad a celite. The filtrate was concentrated. The crude material was purified by chromatography over SiO2 with EtOAc/hexanes (gradient: 0%-40% EtOAc) to afford 32 mg (45%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-methoxy-1-methyl-ethyl)-amide as an off-white solid. [M+Na]+=551.

Workup

  1. customto give a black suspension
  2. customThe system was placed in a sand bath
  3. temperatureThe temperature was maintained for 2 days
  4. temperatureUpon cooling
  5. filtrationthe reaction mixture was filtered through a pad a celite
  6. concentrationThe filtrate was concentrated
  7. customThe crude material was purified by chromatography over SiO2 with EtOAc/hexanes (gradient: 0%-40% EtOAc)

Sources & evidence

ORD record
ord-ab18c104e9b042248b7c68275cafc4d2
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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