Trifluoroacetic acid → 3-(2-(2-((4-(Piperazin-1-ylmethyl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)benzamide

HRID 1473169Notes

Reaction equation

HRID 1473169 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH:40]=[CH:41][CH:42]=1)[CH2:7][CH2:8][C:9]1[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][N:12]=[C:11]([NH:19][C:20]2[CH:39]=[CH:38][C:23]([CH2:24][N:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]3)=[CH:22][CH:21]=2)[N:10]=1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:25]1([CH2:24][C:23]2[CH:22]=[CH:21][C:20]([NH:19][C:11]3[N:10]=[C:9]([CH2:8][CH2:7][C:6]4[CH:5]=[C:4]([CH:42]=[CH:41][CH:40]=4)[C:1]([NH2:2])=[O:3])[C:14]([C:15]([F:17])([F:16])[F:18])=[CH:13][N:12]=3)=[CH:39][CH:38]=2)[CH2:26][CH2:27][NH:28][CH2:29][CH2:30]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71229334tert-Butyl 4-(4-((4-(3-carbamoylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate

Product 1

HCID 682828313-(2-(2-((4-(Piperazin-1-ylmethyl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)benzamideYield 41.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 4-(4-((4-(3-carbamoylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate (I146) (65 mg, 0.11 mmol) was dissolved in DCM (10 mL) then TFA (1 mL) was added and the resulting mixture stirred at room temperature for 18 hours. The volatiles were evaporated under reduced pressure and the residue partitioned between 10% sodium hydroxide (25 mL) and ethyl acetate (25 mL). The aqueous phase was extracted with ethyl acetate (3×25 mL) then the combined ethyl acetate phases washed with brine, dried over sodium sulfate and evaporated. The residue was washed with toluene (2×2 mL) and DCM (2×0.5 mL) to give the title compound (37) (22 mg, 40% yield) as a white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.19 (s, 1H), 8.66 (s, 1H), 7.94 (s, 1H), 7.78 (s, 1H), 7.74-7.64 (m, 3H), 7.40-7.35 (m, 2H), 7.35-7.29 (m, 1H), 7.23 (d, J=8.2 Hz, 2H), 3.38 (s, 2H), 3.17-3.02 (m, 4H), 2.75-2.61 (m, 4H), 2.29 (s, 4H). LCMS Method C: rt 4.52 min; m/z 485.1 [M+H]+; m/z 483.1 [M−H]−.

Workup

  1. customThe volatiles were evaporated under reduced pressure
  2. customthe residue partitioned between 10% sodium hydroxide (25 mL) and ethyl acetate (25 mL)
  3. extractionThe aqueous phase was extracted with ethyl acetate (3×25 mL)
  4. washthe combined ethyl acetate phases washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. washThe residue was washed with toluene (2×2 mL) and DCM (2×0.5 mL)

Sources & evidence

ORD record
ord-adb2cdcb21034b749a9d3ef9a578ef4a
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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