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

HRID 1993687Notes

Reaction equation

HRID 1993687 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].ClC(Cl)(Cl)C[O:24][C:25](=O)[NH:26][C:27]1[N:28]([C:36]2[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=2)[N:29]=[C:30]([C:32]2([CH3:35])[CH2:34][CH2:33]2)[CH:31]=1.C(N(C(C)C)CC)(C)C.O>CS(C)=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:25]([NH:26][C:27]3[N:28]([C:36]4[CH:37]=[CH:38][C:39]([CH3:42])=[CH:40][CH:41]=4)[N:29]=[C:30]([C:32]4([CH3:35])[CH2:33][CH2:34]4)[CH:31]=3)=[O:24])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 17999304tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylateHCID 57832815[5-(1-methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloroethyl ester

Product 1

HCID 591344584-(5-{3-[5-(1-Methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-ureido}-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Heat a solution of 4-(5-amino-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (Preparation 4, 1.05 equiv, 0.5845 g), [5-(1-methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloroethyl ester (Preparation 39, 1.0 equiv, 0.8054 g) and diisopropylethylamine (2 equiv, 0.7 mL) in DMSO (0.25 M, 8 mL) to 60° C. for 6 hours. Cool the resulting mixture to ambient temperature, and add water (20 mL). Extract with EtOAc (2×25 mL), then wash the combined organic phases with water (10 mL) and saturated aq. sodium chloride solution (10 mL). Dry over MgSO4, then subject residue to silica gel chromatography eluting with a gradient 2 M ammonia-methanol in dichloromethane. LCMS(ES+): m/z=532.3 [M+H].

Workup

  1. extractionExtract with EtOAc (2×25 mL)
  2. washwash the combined organic phases with water (10 mL) and saturated aq. sodium chloride solution (10 mL)
  3. dry with materialDry over MgSO4
  4. washsubject residue to silica gel chromatography eluting with a gradient 2 M ammonia-methanol in dichloromethane

Sources & evidence

ORD record
ord-f6648675a0e84196bc684251fb0bf8bb
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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