Sodium Cyanide → {2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-acetonitrile

HRID 1515675Notes

Reaction equation

HRID 1515675 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]2[CH:11]=[C:10]([CH:12]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)[CH2:13][CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[NH:9][C:6]2=[N:7][CH:8]=1.[C-:29]#[N:30].[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH:14]1([CH2:13][CH:12]([C:10]2[NH:9][C:6]3=[N:7][CH:8]=[C:3]([CH2:2][C:29]#[N:30])[CH:4]=[C:5]3[CH:11]=2)[C:19]2[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=2)[CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

5

Reactant 2

HCID 8929Sodium CyanideHCID 672294355-chloromethyl-2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 53251082{2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-acetonitrileYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-chloromethyl-2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (798 mg, 1.92 mmol) and sodium cyanide (500 mg, 10.87 mmol) in N,N-dimethylformamide (3 mL) was subjected to microwave irradiation for 0.5 h at 100° C. The mixture was diluted with ethyl acetate (250 mL), washed with brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 5% methanol/dichloromethane) afforded {2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-acetonitrile (140 mg, 18%) as a light yellow solid: LC/MS m/e calcd for C23H25N3O2S [M+H]+ 408.54, observed 408.0; 1H NMR (400 MHz, CDCl3) δ ppm 1.21 (m, 2H), 1.48 (m, 2H), 1.57-1.90 (m, 5H, H), 2.18 (m, 1H), 2.26 (m, 1H), 3.06 (s, 3H), 3.99 (s, 2H), 4.43 (m, 1H), 6.59 (s, 1H), 7.56 (d, J=8.2 Hz, 2H), 7.90 (d, J=8.2 Hz, 2H), 8.24 (s, 1H), 8.32 (s, 1H), 12.48 (br, 1H).

Workup

  1. customirradiation for 0.5 h at 100° C
  2. washwashed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-cc62791e14334673b8338810a160a767
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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