Phosphorus oxychloride → 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carbonitrile

HRID 1515714Notes

Reaction equation

HRID 1515714 reaction equation
C([NH:5][C:6]([C:8]1[CH:9]=[C:10]2[CH:16]=[C:15]([CH:17]([C:24]3[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=3)[CH2:18][CH:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[NH:14][C:11]2=[N:12][CH:13]=1)=O)(C)(C)C.P(Cl)(Cl)(Cl)=O>C(Cl)(Cl)Cl>[CH:19]1([CH2:18][CH:17]([C:15]2[NH:14][C:11]3=[N:12][CH:13]=[C:8]([C:6]#[N:5])[CH:9]=[C:10]3[CH:16]=2)[C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=2)[CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 672293972-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid tert-butylamide

Product 1

HCID 532512532-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carbonitrileYield 17.4%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid tert-butylamide (240 mg, 0.51 mmol) in chloroform (5 mL) was added phosphorus oxychloride (0.72 mL, 7.71 mmol) at room temperature. The mixture was heated at 80° C. and stirred for 3 h. The resulting mixture was concentrated in vacuo and the residue was extracted with ethyl acetate, washed with a saturated aqueous sodium bicarbonate solution (2×50 mL), brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carbonitrile (35 mg, 14.9%) as a white solid: LC/MS m/e calcd for C22H23N3O2S [M+H]+ 394.51, observed 393.8; 1H NMR (400 MHz, CD3OD) δ ppm 8.42 (s, 1H), 8.26 (d, J=1.5 Hz, 1H), 7.90 (d, J=8.1 Hz, 1H), 7.60 (d, J=8.3 Hz, 1H), 6.54 (s, 1H), 4.34 (t, J=8.0 Hz, 1H), 3.32-3.32 (m, 1H), 3.31 (s, 8H), 3.09 (s, 2H), 2.24-2.32 (m, 1H), 2.10-2.18 (m, 1H), 1.60-1.87 (m, 3H), 1.44-1.55 (m, 1H), 1.17-1.32 (m, 2H).

Workup

  1. concentrationThe resulting mixture was concentrated in vacuo
  2. extractionthe residue was extracted with ethyl acetate
  3. washwashed with a saturated aqueous sodium bicarbonate solution (2×50 mL), brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification

Sources & evidence

ORD record
ord-28a76c4cd27049449ff1139723519aca
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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