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

HRID 1485232Notes

Reaction equation

HRID 1485232 reaction equation
[NH2:1][C:2](=[O:43])[CH2:3][C:4]1[CH:42]=[CH:41][CH:40]=[CH:39][C:5]=1[CH2:6][CH2:7][C:8]1[C:13]([C:14]([F:17])([F:16])[F:15])=[CH:12][N:11]=[C:10]([NH:18][C:19]2[CH:38]=[CH:37][C:22]([CH2:23][N:24]3[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]3)=[CH:21][CH:20]=2)[N:9]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:24]1([CH2:23][C:22]2[CH:21]=[CH:20][C:19]([NH:18][C:10]3[N:9]=[C:8]([CH2:7][CH2:6][C:5]4[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=4[CH2:3][C:2]([NH2:1])=[O:43])[C:13]([C:14]([F:16])([F:15])[F:17])=[CH:12][N:11]=3)=[CH:38][CH:37]=2)[CH2:25][CH2:26][NH:27][CH2:28][CH2:29]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71229653tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate

Product 1

HCID 601648052-(2-(2-(2-((4-(Piperazin-1-ylmethyl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate (I98) (34 mg, 0.057 mmol) was dissolved in DCM (4 mL) and TFA (0.4 mL) was added. The resulting mixture was stirred for 16 hours at room temperature then concentrated under reduced pressure. The residue was suspended in 10% aqueous NaOH (2 mL) and brine (3 mL) then extracted with ethyl acetate (4×5 mL). The combined organic phases were washed with brine, dried (sodium sulphate) and evaporated to dryness. The residue was triturated with diethyl ether to give the title compound (25) (27.5 mg, 98%) as a yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.17 (s, 1H), 8.66 (s, 1H), 7.72-7.66 (m, 2H), 7.26-7.20 (m, 3H), 7.20-7.13 (m, 3H), 6.90 (s, 1H), 3.49 (s, 2H), 3.37 (s, 2H), 3.14-2.98 (m, 4H), 2.67 (t, J=4.7 Hz, 4H), 2.26 (s, 4H). LCMS Method C: rt 4.52 min; m/z 499.1 [M+H]+; m/z 497.1 [M−H]−.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. extractionbrine (3 mL) then extracted with ethyl acetate (4×5 mL)
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried (sodium sulphate)
  5. customevaporated to dryness
  6. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-fee6c6c404b24b21b16eeffca92dfac3
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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