Morpholine → HCID 59054128, compound

HRID 2407995Notes

Reaction equation

HRID 2407995 reaction equation
[CH:1]1([NH:5][S:6]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[NH:15][CH:14]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21](Br)[CH:20]=2)[CH2:13][C:12]3([CH3:27])[CH3:26])(=[O:8])=[O:7])[CH2:4][CH2:3][CH2:2]1.Cl.CN(C)CC(O)=O.[NH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH:1]1([NH:5][S:6]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[NH:15][CH:14]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)[CH:20]=2)[CH2:13][C:12]3([CH3:27])[CH3:26])(=[O:8])=[O:7])[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 70497284HCID 70497284, compound

Product 1

HCID 59054128HCID 59054128, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

The mixture solution of 2-(3-bromo-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-sulfonic acid cyclobutylamide (150.0 mg, 0.34 mmol), copper(I) iodide (20.0 mg, 0.1 mmol), N,N-dimethylglycine hydrochloride (37.5 mg, 0.27 mmol), morpholine (0.78 mL, 9.0 mmol) and potassium carbonate (140.0 mg, 1.0 mmol) in dimethyl sulfoxide (2.0 mL). was stirred at 120° C. for 16 h. Then the reaction mixture was cooled to room temperature and extracted with ethyl acetate (70 mL×2), washed with water (30 mL×3) and saturated aqueous ammonium chloride solution (30 mL×2), dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by 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 4,4-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-sulfonic acid cyclobutylamide (123.7 mg, 80.0%) as a white solid: MS (ESI) M+1=456.2.

Workup

  1. temperatureThen the reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (70 mL×2)
  3. washwashed with water (30 mL×3) and saturated aqueous ammonium chloride solution (30 mL×2)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification by 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)

Sources & evidence

ORD record
ord-bd148cde439346158e4e5b964c10bdfb
Source dataset
uspto-grants-2014_08
Patent number
US08809369B2

Reaction notes

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