Ethyl Acetate → 4-{5-[3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureido]-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1993690Notes

Reaction equation

HRID 1993690 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[C:30]([C:34]1[CH:35]=[C:36]([NH:46][C:47](=O)[O:48]CC(Cl)(Cl)Cl)[N:37]([C:39]2[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=2)[N:38]=1)([CH3:33])([CH3:32])[CH3:31].CCOC(C)=O>CS(C)=O.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:47]([NH:46][C:36]3[N:37]([C:39]4[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=4)[N:38]=[C:34]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH:35]=3)=[O:48])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 17999304tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 685419004-{5-[3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureido]-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl esterYield 85.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

Place 4-(5-amino-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (200 mg, 0.718 mmol), diisopropylethylamine (0.125 mL, 0.718 mmol), and (5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-carbamic acid, 2,2,2-trichloro-ethyl ester (Preparation 38, 291 mg, 0.718 mmol) in DMSO (5 mL) and heat to 75° C. for 17 hours. Cool to room temperature and add EtOAc and water. Separate organic layer and wash with saturated aq. sodium chloride (2×20 mL). Collect organic layer, dry over Mg2SO4, filter, and concentrate under reduced pressure. Subject residue to silica gel chromatography eluting with 0-70% EtOAc:hexane to yield 328 mg (85%) of 4-{5-[3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureido]-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester. MS(ES+): m/z=534.4 [M+H]).

Workup

  1. washSeparate organic layer and wash with saturated aq. sodium chloride (2×20 mL)
  2. dry with materialCollect organic layer, dry over Mg2SO4
  3. filtrationfilter
  4. concentrationconcentrate under reduced pressure
  5. washSubject residue to silica gel chromatography eluting with 0-70% EtOAc

Sources & evidence

ORD record
ord-fa0f13cd7fc44a7bb01f1a45c0616fee
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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