Potassium Cyanide → HCID 178464926, compound

HRID 246004Notes

Reaction equation

HRID 246004 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:23][CH:24]([C@H:26]5[CH2:29][C@H:28](OS(C)(=O)=O)[CH2:27]5)[CH3:25])=[O:22])=[CH:19][N:18]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[C-:43]#[N:44].[K+].C1OCCOCCOCCOCCOCCOC1>CS(C)=O>[C:43]([C@@H:28]1[CH2:29][C@H:26]([CH:24]([NH:23][C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=5)[N:8]([CH3:11])[N:7]=4)[N:13]=3)[N:18]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:40])[CH3:41])[CH:19]=2)=[O:22])[CH3:25])[CH2:27]1)#[N:44]

Participants

5

Reactant 3

HCID 9032Potassium CyanideHCID 2855718-Crown-6HCID 178464932HCID 178464932, compound

Product 1

HCID 178464926HCID 178464926, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methanesulfonic acid trans-3-(1-{[2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-ethyl)-cyclobutyl ester (crude from step 1, 97 mg, 0.16 mmol) in DMSO (1.5 mL) at room temperature was added potassium cyanide (41 mg, 0.63 mmol) and 18-crown-6 (8 mg, 0.03 mmol). The reaction mixture was heated at 100° C. overnight then cooled to room temperature, quenched with water, and extracted with EtOAc (3×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated. The residue was purified via chromatography with 20% to 50% EtOAc/hexanes to isolate 34 mg (40%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(cis-3-cyano-cyclobutyl)-ethyl]-amide as a yellow foam.

Workup

  1. temperaturethen cooled to room temperature
  2. customquenched with water
  3. extractionextracted with EtOAc (3×)
  4. washThe combined organics were washed with water (3×) and brine
  5. dry with materialthen dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified via chromatography with 20% to 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-da36f86769144609a488edae7a3230b6
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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