Potassium Cyanide → HCID 58557736, compound

HRID 1969649Notes

Reaction equation

HRID 1969649 reaction equation
[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[C:19](I)=[CH:18][N:17]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH:29][S:30]([CH:33]2[CH2:35][CH2:34]2)(=[O:32])=[O:31])[CH2:4]1)[CH3:2].[C-:36]#[N:37].[K+]>CN(C=O)C.[Cu]I.C1OCCOCCOCCOCCOCCOC1>[C:36]([C:19]1[C:13]2[N:12]3[C:8]([C@@H:7]4[C@H:3]([CH2:1][CH3:2])[CH2:4][C@H:5]([NH:29][S:30]([CH:33]5[CH2:35][CH2:34]5)(=[O:32])=[O:31])[CH2:6]4)=[N:9][N:10]=[C:11]3[CH:16]=[N:15][C:14]=2[N:17]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:27])([CH3:26])[CH3:28])[CH:18]=1)#[N:37]

Participants

6

Reactant 2

HCID 9032Potassium CyanideHCID 58557818HCID 58557818, compound

Product 1

HCID 58557736HCID 58557736, compoundYield 82%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 2855718-Crown-6CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of N-((1S,3R,4S)-3-ethyl-4-(8-iodo-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)cyclopropanesulfonamide (0.1 g, 0.16 mmol, prepared using KK from Preparation #GGG.1) in DMF (1.2 mL) was added potassium cyanide (0.03 g, 0.40 mmol), copper(I) iodide (0.076 g, 0.40 mmol), tetrakis(triphenyl-phosphine)palladium(0) (0.002 g, 0.002 mmol) and 18-crown-6 (0.003 g, 0.01 mmol). The reaction mixture was stirred at about 110° C. for about 4 h and cooled to ambient temperature. The solvent was removed under reduced pressure. The residue was partitioned between EtOAc (15 mL) and water (8 mL). The aqueous layer was further extracted with EtOAc (15 mL). The combined organic layers were dried with MgSO4, filtered, and concd under reduced pressure to give N-((1S,3S,4R)-3-(8-cyano-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)-4-ethylcyclopentyl)cyclopropanesulfonamide (0.069 g, 82%): LC/MS (Table 1, Method b) Rt=2.50 min; MS m/z: 530 (M+H)+.

Workup

  1. temperaturecooled to ambient temperature
  2. customThe solvent was removed under reduced pressure
  3. customThe residue was partitioned between EtOAc (15 mL) and water (8 mL)
  4. extractionThe aqueous layer was further extracted with EtOAc (15 mL)
  5. dry with materialThe combined organic layers were dried with MgSO4
  6. filtrationfiltered

Sources & evidence

ORD record
ord-eccb9288bce44b37b216bacf324e165b
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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