Diisopropylethylamine → 1-{6-[4-(2,6-difluoro-benzoyl)-piperazin-1-yl]-5-methyl-pyridin-3-yl}-3-[5-(2-fluoro-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea

HRID 1993711Notes

Reaction equation

HRID 1993711 reaction equation
CCN(C(C)C)C(C)C.[NH2:10][C:11]1[CH:12]=[C:13]([CH3:33])[C:14]([N:17]2[CH2:22][CH2:21][N:20]([C:23]([C:25]3[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=3[F:32])=[O:24])[CH2:19][CH2:18]2)=[N:15][CH:16]=1.ClC(Cl)(Cl)C[O:37][C:38](=O)[NH:39][C:40]1[N:41]([C:50]2[CH:55]=[CH:54][C:53]([CH3:56])=[CH:52][CH:51]=2)[N:42]=[C:43]([C:45]([CH3:49])([CH3:48])[CH2:46][F:47])[CH:44]=1>C(#N)C>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[C:23]([N:20]1[CH2:19][CH2:18][N:17]([C:14]2[N:15]=[CH:16][C:11]([NH:10][C:38]([NH:39][C:40]3[N:41]([C:50]4[CH:55]=[CH:54][C:53]([CH3:56])=[CH:52][CH:51]=4)[N:42]=[C:43]([C:45]([CH3:49])([CH3:48])[CH2:46][F:47])[CH:44]=3)=[O:37])=[CH:12][C:13]=2[CH3:33])[CH2:22][CH2:21]1)=[O:24]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 68540113[4-(5-Amino-3-methyl-pyridin-2-yl)-piperazin-1-yl]-(2,6-difluoro-phenyl)-methanoneHCID 68540645[5-(2-fluoro-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

Product 1

HCID 591344441-{6-[4-(2,6-difluoro-benzoyl)-piperazin-1-yl]-5-methyl-pyridin-3-yl}-3-[5-(2-fluoro-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-ureaYield 48%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Add DIEA (2 equiv.) to a solution of [4-(5-amino-3-methyl-pyridin-2-yl)-piperazin-1-yl]-(2,6-difluoro-phenyl)-methanone (400 mg, 1.205 mmol) and [5-(2-fluoro-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester (1 equiv) in acetonitrile (12 mL). Stir the mixture at 80° C. in a sealed tube. After 4 days, remove solvent. Dilute crude with DCM, extract with water, and dry over Na2SO4. Filter and remove solvent under reduced pressure. Subject solid to silica gel chromatography, eluting with hexane/acetone 3:1 to obtain 352 mg of 1-{6-[4-(2,6-difluoro-benzoyl)-piperazin-1-yl]-5-methyl-pyridin-3-yl}-3-[5-(2-fluoro-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea as a white solid (48% yield). ES+(m/z): 606 [M+1]

Workup

  1. customremove solvent
  2. additionDilute crude with DCM
  3. extractionextract with water
  4. dry with materialdry over Na2SO4
  5. filtrationFilter
  6. customremove solvent under reduced pressure
  7. washeluting with hexane/acetone 3:1

Sources & evidence

ORD record
ord-886edfdb7d06477dbad84e8ce2b560c5
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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