N-Aminomorpholine → HCID 66740466, compound

HRID 1627279Notes

Reaction equation

HRID 1627279 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([S:23][CH2:24][C:25]3[C:30]([F:31])=[CH:29][C:28]([S:32]([NH:35][C:36](=[O:40])OCC)(=[O:34])=[O:33])=[CH:27][C:26]=3[F:41])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:42][CH3:43].[NH2:44][N:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=3)[C:14]([S:23][CH2:24][C:25]3[C:26]([F:41])=[CH:27][C:28]([S:32]([NH:35][C:36](=[O:40])[NH:44][N:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)(=[O:34])=[O:33])=[CH:29][C:30]=3[F:31])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:42][CH3:43]

Participants

5

Reactant 2

HCID 20315N-AminomorpholineHCID 66739854Ethyl 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonylcarbamate

Product 1

HCID 66740466HCID 66740466, compoundYield 46.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonylcarbamate (76 mg, 0.12 mmol, 1.0 eq) and 4-aminomorpholine (0.045 mL, 0.46 mmol, 4.0 eq) in toluene (2.5 mL, anhyd) were heated at reflux for 2.5 h. The reaction mixture was cooled to room temperature, diluted with EtOAc and washed with water, followed by brine. After drying (MgSO4), the organics were concentrated and purified by chromatography (silica, 0 to 80% EtOAc/Hex, then 10% MeOH/DCM) to provide the title compound (40 mg). 1H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 7.41-7.16 (m, 4H), 7.03-6.90 (m, 3H), 6.57-6.43 (m, 4H), 4.02-3.98 (m, 2H), 3.71-3.65 (m, 3H), 3.57-3.50 (m, 3H), 3.48-3.38 (m, 1H), 3.31-3.25 (m, 1H), 2.69-2.58 (m, 3H), 1.46 (s, 6H); MS (EI) m/z 710.1 (MH+).

Workup

  1. temperatureat reflux for 2.5 h
  2. washwashed with water
  3. dry with materialAfter drying (MgSO4)
  4. concentrationthe organics were concentrated
  5. custompurified by chromatography (silica, 0 to 80% EtOAc/Hex

Sources & evidence

ORD record
ord-81b4184b03ee480ca010d837eeca4a6e
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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