Water → HCID 11634218, compound

HRID 499202Notes

Reaction equation

HRID 499202 reaction equation
ClC(Cl)(Cl)CO[C:5](=[O:17])[NH:6][C:7]1[N:8]([CH3:16])[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([O:33][C:34]2[CH:39]=[CH:38][C:37]([NH2:40])=[CH:36][CH:35]=2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C(N(CC)C(C)C)(C)C.O>CS(C)=O.ClCCl>[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:40][C:37]2[CH:38]=[CH:39][C:34]([O:33][CH:30]3[CH2:29][CH2:28][N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[CH2:32][CH2:31]3)=[CH:35][CH:36]=2)=[O:17])[N:8]([CH3:16])[N:9]=1)([CH3:13])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 22181157tert-Butyl 4-(4-aminophenoxy)piperidine-1-carboxylateHCID 594208722,2,2-Trichloroethyl (3-tert-butyl-1-methyl-1H-pyrazol-5-yl)carbamate

Product 1

HCID 11634218HCID 11634218, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

Nitrogen gas is bubbled through a solution of (5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (1.65 g, 5.01 mmol) and 4-(4-amino-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester (1.47 g, 5.02 mmol) in DMSO (20 mL) for 2 min. Next, N,N-diisopropylethylamine (2 mL, 11.48 mmol) is added. The reaction mixture is stirred at 60° C. for 6 hours. Then, the reaction mixture is distributed between water (150 mL) and dichloromethane (100 mL). The aqueous layer is isolated and extracted with dichloromethane (2×100 mL). The combined organic phases are washed with water (100 mL) and aqueous sodium chloride (100 mL), and dried over anhydrous sodium sulfate. After removal of solvent, the crude product is purified on a silica gel chromatography with ethyl acetate-hexanes (25%) to give a white solid (2.28 g, 97%, ES−(m/z) 470.1 [M−H]).

Workup

  1. customThe aqueous layer is isolated
  2. extractionextracted with dichloromethane (2×100 mL)
  3. washThe combined organic phases are washed with water (100 mL) and aqueous sodium chloride (100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customAfter removal of solvent
  6. customthe crude product is purified on a silica gel chromatography with ethyl acetate-hexanes (25%)
  7. customto give a white solid (2.28 g, 97%, ES−(m/z) 470.1 [M−H])

Sources & evidence

ORD record
ord-3901c7dee0d34ea6801aa2ce7f54ff47
Source dataset
uspto-grants-2010_08
Patent number
US07767674B2

Reaction notes

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