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

HRID 1993695Notes

Reaction equation

HRID 1993695 reaction equation
ClC(Cl)(Cl)C[O:4][C:5](=O)[NH:6][C:7]1[N:8]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)[N:9]=[C:10]([C:12]([CH2:16][F:17])([CH3:15])[CH2:13][F:14])[CH:11]=1.CCN(C(C)C)C(C)C.[C:37]([O:41][C:42]([N:44]1[CH2:49][CH2:48][N:47]([C:50]2[CH:55]=[CH:54][C:53]([NH2:56])=[C:52]([CH3:57])[N:51]=2)[CH2:46][CH2:45]1)=[O:43])([CH3:40])([CH3:39])[CH3:38].O>CS(C)=O>[C:37]([O:41][C:42]([N:44]1[CH2:49][CH2:48][N:47]([C:50]2[CH:55]=[CH:54][C:53]([NH:56][C:5]([NH:6][C:7]3[N:8]([C:18]4[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=4)[N:9]=[C:10]([C:12]([CH2:13][F:14])([CH3:15])[CH2:16][F:17])[CH:11]=3)=[O:4])=[C:52]([CH3:57])[N:51]=2)[CH2:46][CH2:45]1)=[O:43])([CH3:40])([CH3:39])[CH3:38]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 591344511-Boc-4-(5-amino-6-methyl-2-pyridinyl)piperazineHCID 68538054[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

Product 1

HCID 685370594-(5-{3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-ureido}-6-methyl-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
85 °C

Procedure

Add [5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester (2.7 mmol, 1.2 g) and DIEA (2.9 mmol, 0.5 mL) over a solution of 4-(5-amino-6-methyl-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (2.9 mmol, 0.9 g) in 4 mL of DMSO and stir at 85° C. overnight. Cool down, add water and extract with CH2Cl2. Combine the organic layers and wash with saturated aq. sodium chloride solution. Dry over sodium sulfate, filter, and concentrate under reduced pressure to give 4-(5-{3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-ureido}-6-methyl-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester. Subject residue to silica gel chromatography eluting with hexanes/ethyl acetate in gradient (from 10 to 50%). MS(ES+): m/z=584 [M+H]).

Workup

  1. temperatureCool down,
  2. extractionextract with CH2Cl2
  3. washwash with saturated aq. sodium chloride solution
  4. dry with materialDry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-e96b4fe7c4a4476bacea41cb81ea353f
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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