Trifluoroacetic acid → 2-Methyl-5-(2-(2-((4-(piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)benzamide

HRID 1485206Notes

Reaction equation

HRID 1485206 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH:39]=[CH:40][C:41]=1[CH3:42])[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:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[N:10]=1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:42][C:41]1[CH:40]=[CH:39][C:6]([CH2:7][CH2:8][C:9]2[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][N:12]=[C:11]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)=[CH:22][CH:21]=3)[N:10]=2)=[CH:5][C:4]=1[C:1]([NH2:2])=[O:3]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68282839Tert-butyl 4-(4-((4-(3-carbamoyl-4-methylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

Product 1

HCID 601646992-Methyl-5-(2-(2-((4-(piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)benzamideYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To tert-butyl 4-(4-((4-(3-carbamoyl-4-methylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I73) (0.029 g, 0.054 mmol) in DCM (2 mL) was added TFA (0.100 mL, 1.36 mmol) and the mixture stirred overnight (16 hours) at room temperature. The resulting mixture was then concentrated under reduced pressure and the residue taken up in EtOAc (10 mL). The resulting organic suspension was washed with 10% aqueous NaOH (10 mL) and the aqueous layer extracted with EtOAc (2×10 mL). The combined organics were washed with water (15 mL) then concentrated under reduced pressure. The residue was taken up in DCM (4 mL) and TFA (0.200 mL) and stirred overnight (16 hours). The resulting mixture was concentrated under reduced pressure then diluted with EtOAc (15 mL). The resulting solution was washed with 10% aqueous NaOH (15 mL) then the aqueous layer was extracted with EtOAc (15 mL). The combined organic extracts were washed with water (20 mL) then dried using a phase separation cartridge before concentrating under reduced pressure to give the title compound (19) (5.1 mg, 21%); 1H NMR (400 MHz, d6-DMSO) δ 9.96 (s, 1H), 8.60 (s, 1H), 7.67 (s, 1H), 7.53 (d, J=9.0 Hz, 2H), 7.33 (s, 1H), 7.25 (s, 1H), 7.16 (m, 2H), 6.90 (d, J=9.1 Hz, 2H), 3.01 (m, 8H), 2.83 (m, 4H), 2.32 (s, 3H). LCMS Method C: rt 4.76 min; m/z 485.1 [M+H]+.

Workup

  1. concentrationThe resulting mixture was then concentrated under reduced pressure
  2. washThe resulting organic suspension was washed with 10% aqueous NaOH (10 mL)
  3. extractionthe aqueous layer extracted with EtOAc (2×10 mL)
  4. washThe combined organics were washed with water (15 mL)
  5. concentrationthen concentrated under reduced pressure
  6. stirringTFA (0.200 mL) and stirred overnight (16 hours)
  7. concentrationThe resulting mixture was concentrated under reduced pressure
  8. additionthen diluted with EtOAc (15 mL)
  9. washThe resulting solution was washed with 10% aqueous NaOH (15 mL)
  10. extractionthe aqueous layer was extracted with EtOAc (15 mL)
  11. washThe combined organic extracts were washed with water (20 mL)
  12. customthen dried
  13. customa phase separation cartridge
  14. concentrationbefore concentrating under reduced pressure

Sources & evidence

ORD record
ord-ff6ec3eea2844a55aee2000a3badbf14
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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