Phosphorus oxychloride → 4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-benzonitrile

HRID 1515712Notes

Reaction equation

HRID 1515712 reaction equation
C([NH:5][C:6](=O)[C:7]1[CH:12]=[CH:11][C:10]([CH:13]([C:20]2[NH:29][C:23]3=[N:24][CH:25]=[C:26]([F:28])[CH:27]=[C:22]3[CH:21]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:9][CH:8]=1)(C)(C)C.P(Cl)(Cl)(Cl)=O>C(Cl)(Cl)Cl>[CH:15]1([CH2:14][CH:13]([C:10]2[CH:11]=[CH:12][C:7]([C:6]#[N:5])=[CH:8][CH:9]=2)[C:20]2[NH:29][C:23]3=[N:24][CH:25]=[C:26]([F:28])[CH:27]=[C:22]3[CH:21]=2)[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 67228592N-tert-butyl-4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-benzamide

Product 1

HCID 532512514-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-benzonitrileYield 59%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of N-tert-butyl-4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-benzamide (250 mg, 0.61 mmol) in chloroform (6 mL) at room temperature was added phosphorus oxychloride (0.32 mL, 3.15 mmol). 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 4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-benzonitrile (120 mg, 58.8%) as a white solid: LC/MS m/e calcd for C21H20FN3 [M+H]+ 334.41, observed 334.1; 1H NMR (400 MHz, CD3OD) δ ppm 8.01 (s, 1H), 7.63-7.70 (m, 3H), 7.53 (d, J=8.3 Hz, 2H), 6.39 (s, 1H), 4.28 (t, J=7.8 Hz, 1H), 2.23-2.31 (m, 1H), 2.03-2.13 (m, 1H), 1.61-1.87 (m, 5H), 1.51 (dd, J=7.3, 4.0 Hz, 2H), 1.17-1.35 (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-708391f51c4f44e1a07f65332da61385
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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