Triethylamine → 1-[4-(3-Amino-phenyl)-piperidin-1-yl]-2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone

HRID 403363Notes

Reaction equation

HRID 403363 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]([OH:10])=O)[N:5]=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:3]=1.C(N(CC)CC)C.Cl.[NH:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=2)[CH2:25][CH2:24]1>CN(C=O)C>[NH2:35][C:31]1[CH:30]=[C:29]([CH:26]2[CH2:27][CH2:28][N:23]([C:8](=[O:10])[CH2:7][N:6]3[C:2]([CH3:1])=[CH:3][C:4]([C:11]([F:14])([F:13])[F:12])=[N:5]3)[CH2:24][CH2:25]2)[CH:34]=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 5961182-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetic acidHCID 23103412Benzenamine, 3-(4-piperidinyl)-, hydrochloride (1:?)

Product 1

HCID 682800461-[4-(3-Amino-phenyl)-piperidin-1-yl]-2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid (0.49 g, 2.35 mmol) in DMF (10 mL) is added triethylamine (0.65 mL, 4.7 mmol), followed by 1-hydroxy-7-benzotriazole (0.32 g, 2.35 mmol) and 1-Ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (0.45 g, 2.35 mmol). After stirring 15 min at RT, 3-Piperidin-4-yl-phenylamine hydrochloride (0.50 g, 2.35 mmol) is added to the reaction mixture. After stirring overnight at RT, solvent is evaporated and the resulting yellow oil is dissolved in ethylacetate (20 mL), washed with saturated aqueous sodium bicarbonate solution (20 mL), and brine (20 mL). The organic layer is dried over sodium sulfate, filtered, and evaporated under reduced pressure to give 1-[4-(3-amino-phenyl)-piperidin-1-yl]-2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone as a crude mixture of good enough purity for the next step (0.86 g, quantitative). 1H-NMR (400 MHz, MeOD): δ=1.52-1.63 (m, 1H), 1.64-1.73 (m, 1H), 1.80-1.93 (m, 2H), 2.33 (s, 3H), 2.68-2.81 (m, 2H), 2.99 (s, 2H), 3.21-3.27 (m, 1H), 4.02-4.09 (m, 1H), 4.55-4.62 (m, 1H), 5.12-5.28 (q, 2H), 6.41 (s, 1H), 6.55-6.60 (m, 1H), 6.61-6.62 (m, 1H), 7.00-7.07 (t, 1H), 7.99 (s, 1H). MS: m/z=367 (M+1).

Workup

  1. stirringAfter stirring overnight at RT
  2. customsolvent is evaporated
  3. dissolutionthe resulting yellow oil is dissolved in ethylacetate (20 mL)
  4. washwashed with saturated aqueous sodium bicarbonate solution (20 mL), and brine (20 mL)
  5. dry with materialThe organic layer is dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-9a98cb7221fa4c16b19982921027c3a1
Source dataset
uspto-grants-2014_06
Patent number
US08748432B2

Reaction notes

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