4-Methylmorpholine → 2-(4-Methylpiperazin-1-yl)ethyl {3-[1-(5,6-difluoro-2-oxo-benzoxazol-3-yl)ethyl]phenyl}carbamate

HRID 1970863Notes

Reaction equation

HRID 1970863 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]([N:10]2[C:14]3[CH:15]=[C:16]([F:20])[C:17]([F:19])=[CH:18][C:13]=3[O:12][C:11]2=[O:21])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][OH:31])[CH2:25][CH2:24]1.CN1CC[O:36][CH2:35]C1.C(=O)(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl>ClCCl>[F:20][C:16]1[C:17]([F:19])=[CH:18][C:13]2[O:12][C:11](=[O:21])[N:10]([CH:8]([C:4]3[CH:3]=[C:2]([NH:1][C:35](=[O:36])[O:31][CH2:30][CH2:29][N:26]4[CH2:27][CH2:28][N:23]([CH3:22])[CH2:24][CH2:25]4)[CH:7]=[CH:6][CH:5]=3)[CH3:9])[C:14]=2[CH:15]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 94429TriphosgeneHCID 2311841-(2-Hydroxyethyl)-4-methylpiperazineHCID 584861083-[1-(3-aminophenyl)ethyl]-5,6-difluoro-3H-benzoxazol-2-one

Product 1

HCID 251240982-(4-Methylpiperazin-1-yl)ethyl {3-[1-(5,6-difluoro-2-oxo-benzoxazol-3-yl)ethyl]phenyl}carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

250 mg (0.86 mmol) of 3-[1-(3-aminophenyl)ethyl]-5,6-difluoro-3H-benzoxazol-2-one, 137 mg (0.95 mmol) of 2-(4-methylpiperazin-1-yl)ethanol and 200 μl (1.81 mmol) of N-methylmorpholine are suspended in 10 ml of dichloromethane, the mixture is stirred at room temperature for 10 min, and 128 mg (0.43 mmol) of bis(trichloromethyl) carbonate are added. The reaction mixture is stirred at room temperature for 16 h. The mixture is subsequently diluted with 30 ml of dichloromethane, washed with 2×20 ml of saturated sodium hydrogencarbonate solution, dried over sodium sulfate and evaporated to dryness. The crude product is purified by column chromatography on silica gel, dissolved in acetone, warmed with HCl in ether and, when crystallisation is complete, filtered off with suction and dried. Product (“A27”): 95 mg, product is in the form of the hydrochloride;

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 16 h
  2. washwashed with 2×20 ml of saturated sodium hydrogencarbonate solution
  3. dry with materialdried over sodium sulfate
  4. customevaporated to dryness
  5. customThe crude product is purified by column chromatography on silica gel
  6. dissolutiondissolved in acetone
  7. temperaturewarmed with HCl in ether and, when crystallisation
  8. filtrationfiltered off with suction
  9. customdried

Sources & evidence

ORD record
ord-264090f323ad43aa9d72c222465be7ca
Source dataset
uspto-grants-2013_04
Patent number
US08431572B2

Reaction notes

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