Sodium Hydroxide → HCID 53249981, compound

HRID 1515879Notes

Reaction equation

HRID 1515879 reaction equation
[ClH:1].[CH3:2][S:3]([C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:20]2[NH:29][C:23]3=[N:24][CH:25]=[C:26](N)[CH:27]=[C:22]3[CH:21]=2)[CH2:13][CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:8][CH:7]=1)(=[O:5])=[O:4].N([O-])=O.[Na+].[OH-].[Na+]>Cl.O.[Cu]Cl>[Cl:1][C:26]1[CH:27]=[C:22]2[CH:21]=[C:20]([CH:12]([C:9]3[CH:10]=[CH:11][C:6]([S:3]([CH3:2])(=[O:5])=[O:4])=[CH:7][CH:8]=3)[CH2:13][CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[NH:29][C:23]2=[N:24][CH:25]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 23668193Sodium NitriteHCID 67229143HCID 67229143, compound

Product 1

HCID 53249981HCID 53249981, compoundYield 11.4%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-[1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-ylamine hydrochloride (454 mg, 1.05 mmol) in concentrated hydrochloric acid (6 mL) at 0° C. was added a solution of sodium nitrite (360 mg, 5.25 mmol) in water (3 mL) dropwise. After stirring for 10 min at 0° C., a solution of copper (I) chloride (310 mg, 3.15 mmol) in concentrated hydrochloric acid (3 mL) was added. After stirring for another 10 min at 60° C., the mixture was treated with 20% sodium hydroxide solution (pH 8), 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-[1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (50 mg, 11%): LC/MS m/e calcd for C21H23ClN2O3S [M+H]+ 419.95, observed 419.3; 1H NMR (400 MHz, CD3OD) δ ppm 8.06 (s, 1H), 7.87-7.92 (m, 3H), 7.60 (d, J=8.1 Hz, 2H), 6.39 (s, 1H), 4.43 (t, J=8.0 Hz, 1H), 3.85-3.92 (m, 2H), 3.21-3.29 (m, 2H), 3.09 (s, 3H), 2.18-2.26 (m, 1H), 1.98-2.06 (m, 1H), 1.62-1.75 (m, 2H), 1.30-1.51 (m, 3H).

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-ae61d4d7020a4b899339603b31044754
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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