Cesium carbonate → 1-(2-isopropylphenyl)-3-(3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propyl)urea

HRID 62072

Reaction equation

HRID 62072 reaction equation
[CH:1]([C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH2:6])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[N-:28]=[C:29]=[O:30].[F:31][C:32]([F:56])([F:55])[O:33][C:34]1[CH:39]=[CH:38][C:37]([N:40]2[CH:44]=[N:43][C:42]([C:45]3[CH:50]=[CH:49][C:48]([CH2:51][CH2:52][CH2:53]N)=[CH:47][CH:46]=3)=[N:41]2)=[CH:36][CH:35]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>ClCCl.O.C(#N)C>[CH:1]([C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH:6][C:29]([NH:28][CH2:53][CH2:52][CH2:51][C:48]1[CH:47]=[CH:46][C:45]([C:42]2[N:43]=[CH:44][N:40]([C:37]3[CH:38]=[CH:39][C:34]([O:33][C:32]([F:56])([F:31])[F:55])=[CH:35][CH:36]=3)[N:41]=2)=[CH:50][CH:49]=1)=[O:30])([CH3:3])[CH3:2]

Participants

10

Reactant 6

HCID 10796Cesium carbonateHCID 125612-IsopropylanilineHCID 94429TriphosgeneHCID 105034IsocyanateHCID 516892Sodium BicarbonateHCID 904042683-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propan-1-amine

Product 1

HCID 1186750951-(2-isopropylphenyl)-3-(3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propyl)ureaYield 16%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Procedure

To 2-isopropylaniline (0.50 g, 3.7 mmol) and sodium bicarbonate (0.93 g, 11 mmol) in dichloromethane and water (36 mL, 2:1) was added triphosgene (0.55 g, 1.9 mmol) at 0° C. The reaction was stirred until complete conversion to the isocyanate, as observed by thin layer chromatography. The reaction was then diluted with dichloromethane (100 mL), and the organic layer was separated from the water layer and concentrated. The residue obtained was dissolved in acetonitrile (15 mL) and 3-(4-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propan-1-amine (1.2 g, 3.4 mmol) and cesium carbonate (1.1 g, 3.4 mmol) were added. The reaction was stirred at room temperature for 16 hours. The reaction was quenched with water (50 mL) and extracted with dichloromethane (3×100 mL). The organic layers were dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using high pressure liquid chromatography provided the title compound as an off-white solid (0.26 g, 16%).

Workup

  1. customthe organic layer was separated from the water layer
  2. concentrationconcentrated
  3. customThe residue obtained
  4. customThe reaction was quenched with water (50 mL)
  5. extractionextracted with dichloromethane (3×100 mL)
  6. dry with materialThe organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-da2468c4aa91404388d54bd8211891cb
Source dataset
uspto-grants-2016_09
Patent number
US09445594B2

Linked notes

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