Potassium Cyanide → HCID 178464927, compound

HRID 245998Notes

Reaction equation

HRID 245998 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 178464931HCID 178464931, compound

Product 1

HCID 178464927HCID 178464927, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methanesulfonic acid cis-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, 114 mg, 0.19 mmol) in DMSO (1.5 mL) at room temperature was added potassium cyanide (48 mg, 0.74 mmol). The reaction mixture was heated at 60° C. for 2.5 h. 18-Crown-6 (10 mg, 0.04 mmol) was added and heated was continued at 80° C. for 2 h then at 100° C. overnight. The reaction was 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 30% to 50% EtOAc/hexanes to isolate 46 mg (45%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(trans-3-cyano-cyclobutyl)-ethyl]-amide as a yellow foam.

Workup

  1. temperatureheated
  2. customat 100° C.
  3. customovernight
  4. temperatureThe reaction was cooled to room temperature
  5. customquenched with water
  6. extractionextracted with EtOAc (3×)
  7. washThe combined organics were washed with water (3×) and brine
  8. dry with materialthen dried over MgSO4
  9. concentrationconcentrated
  10. customThe residue was purified via chromatography with 30% to 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-9d307709d14247b394fa1b3103db3c5a
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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