Water → (4-{6-Amino-5-[1-(2-trifluoromethyl-phenyl)-ethoxy]-pyridin-3-yl)-phenyl)-(3,5-dimethyl-piperazin-1-yl)-methanone

HRID 425902Notes

Reaction equation

HRID 425902 reaction equation
C(OC([N:8]1[CH:13]([CH3:14])[CH2:12][N:11]([C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:23]=[N:24][C:25]([NH2:29])=[C:26]([OH:28])[CH:27]=3)=[CH:18][CH:17]=2)[CH2:10][CH:9]1[CH3:31])=O)(C)(C)C.Br[CH:33]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[C:41]([F:44])([F:43])[F:42])[CH3:34].C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[NH2:29][C:25]1[N:24]=[CH:23][C:22]([C:19]2[CH:18]=[CH:17][C:16]([C:15]([N:11]3[CH2:10][CH:9]([CH3:31])[NH:8][CH:13]([CH3:14])[CH2:12]3)=[O:30])=[CH:21][CH:20]=2)=[CH:27][C:26]=1[O:28][CH:33]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[C:41]([F:42])([F:43])[F:44])[CH3:34]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27756211-(1-Bromoethyl)-2-(trifluoromethyl)benzeneHCID 667018204-[4-(6-Amino-5-hydroxy-pyridin-3-yl)-benzoyl]-2,6-dimethyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 21110919(4-{6-Amino-5-[1-(2-trifluoromethyl-phenyl)-ethoxy]-pyridin-3-yl)-phenyl)-(3,5-dimethyl-piperazin-1-yl)-methanoneYield 34.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 4-[4-(6-Amino-5-hydroxy-pyridin-3-yl)-benzoyl]-2,6-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (50 mg, 0.12 mmol) and 1-(1-bromo-ethyl)-2-trifluoromethyl-benzene (32 mg, 0.12 mmol) in DMF (2 ml) was added 2 M Cs2CO3 (0.18 mL, 0.35 mmol), followed by water (0.5 mL), the mixture was stirred overnight then heated at 70° C. for 8 hr, LCMS showed that the reaction was completed. The DMF and water were removed. TFA (2 mL was added to the residue and stirred at room temperature for 3 hr. The TFA was removed, followed by addition of methanol. The residue was purified by prep-HPLC to afford (4-{6-amino-5-[1-(2-trifluoromethyl-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-(3,5-dimethyl-piperazin-1-yl)-methanone (20 mg, yield 34.2%).

Workup

  1. customThe DMF and water were removed
  2. additionTFA (2 mL was added to the residue
  3. stirringstirred at room temperature for 3 hr
  4. customThe TFA was removed
  5. additionfollowed by addition of methanol
  6. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-170d98bb5efc423f9cb3541dd2623efa
Source dataset
uspto-grants-2012_01
Patent number
US08106197B2

Reaction notes

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