Sodium Hydroxide → 5-chloro-2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine

HRID 1515861Notes

Reaction equation

HRID 1515861 reaction equation
[ClH:1].[CH:2]1([CH2:7][CH:8]([C:19]2[NH:28][C:22]3=[N:23][CH:24]=[C:25](N)[CH:26]=[C:21]3[CH:20]=2)[C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:11][CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3]1.N([O-])=O.[Na+].[OH-].[Na+]>Cl.O.[Cu]Cl>[Cl:1][C:25]1[CH:26]=[C:21]2[CH:20]=[C:19]([CH:8]([C:9]3[CH:14]=[CH:13][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:11][CH:10]=3)[CH2:7][CH:2]3[CH2:6][CH2:5][CH2:4][CH2:3]3)[NH:28][C:22]2=[N:23][CH:24]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 23668193Sodium NitriteHCID 67229247HCID 67229247, compound

Product 1

HCID 532499825-chloro-2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridineYield 30%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-ylamine hydrochloride (prepared as in Example 107, 327 mg, 0.78 mmol) in concentrated hydrochloric acid (5 mL) at 0° C. was added a solution of sodium nitrite (270 mg, 3.9 mmol) in water (3 mL) dropwise. After stirring for 10 min at 0° C., a solution of copper (I) chloride (232 mg, 2.34 mmol) in concentrated hydrochloric acid (3 mL) was added. After stirring for another 10 min at 60° C., the mixture was adjusted to pH 8 with a 20% aqueous sodium hydroxide solution, extracted with dichloromethane, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified 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) to afford 5-chloro-2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (94 mg, 30%): LC/MS m/e calcd for C21H23ClN2O2S [M+H]+ 403.95, observed 403.3; 1H NMR (400 MHz, CD3OD) δ ppm 1.22 (m, 2H), 1.49 (m, 2H), 1.60-1.88 (m, 5H, H), 2.11 (m, 1H), 2.26 (m, 1H), 3.08 (s, 3H), 4.30 (t, J=7.9 Hz, 1H), 6.37 (s, 1H), 7.59 (d, J=8.4 Hz, 2H), 7.88 (s, 1H), 7.89 (d, J=8.4 Hz, 2H), 8.05 (br, 1H).

Workup

  1. stirringAfter stirring for another 10 min at 60° C.
  2. extractionextracted with dichloromethane
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified

Sources & evidence

ORD record
ord-2e986d13c8fd40c0b93b7ba2bbcaf671
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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