Diethyl Ether → 4-{5-[3-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureido]-6-methyl-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1993688Notes

Reaction equation

HRID 1993688 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])=[C:16]([CH3:21])[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22]([C:26]1[CH:27]=[C:28]([NH:38][C:39](=O)[O:40]CC(Cl)(Cl)Cl)[N:29]([C:31]2[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=2)[N:30]=1)([CH3:25])([CH3:24])[CH3:23].CCN(C(C)C)C(C)C.C(OCC)C>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:39]([NH:38][C:28]3[N:29]([C:31]4[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=4)[N:30]=[C:26]([C:22]([CH3:25])([CH3:24])[CH3:23])[CH:27]=3)=[O:40])=[C:16]([CH3:21])[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 591344511-Boc-4-(5-amino-6-methyl-2-pyridinyl)piperazine

Product 1

HCID 685368704-{5-[3-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureido]-6-methyl-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl esterYield 89%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Heat a solution of 4-(5-amino-6-methyl-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (Preparation 3, 41.20 g, 140.9 mmol), (5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-carbamic acid, 2,2,2-trichloro-ethyl ester (Preparation 38, 57.03 g, 140.9 mmol), and DIEA (36.8 mL, 211.4 mmol) in DMSO (500 mL) at 60-65° C. for 2.5 hours. Add additional DMSO (100 mL) during the last 30 min to the thick slurry. Cool the slurry to room temperature and allow to stand overnight. Add diethyl ether (600 mL) and stir the slurry for 1 hour at room temperature. Filter and wash with diethyl ether (5×300 mL) then air-dry to afford a white solid (68.70 g, 89% yield uncorrected for DMSO—contains ca. 85 mol % of DMSO. LCMS(ES+): m/z=548 [M+H].

Workup

  1. filtrationFilter
  2. washwash with diethyl ether (5×300 mL)
  3. customthen air-dry
  4. customto afford a white solid (68.70 g, 89% yield uncorrected for DMSO—contains ca. 85 mol % of DMSO. LCMS(ES+)

Sources & evidence

ORD record
ord-6f3675c6de2f4513abe105e261972924
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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