Trifluoroacetic acid → 1-(2-(2-(2-((4-(1-Aminoethyl)phenyl)amino)-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592444Notes

Reaction equation

HRID 592444 reaction equation
[C:1]([C:4]1([C:7]2[CH:38]=[CH:37][CH:36]=[CH:35][C:8]=2[CH2:9][CH2:10][C:11]2[C:16]([CH3:17])=[CH:15][N:14]=[C:13]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH:25]([NH:27]C(=O)OC(C)(C)C)[CH3:26])=[CH:21][CH:20]=3)[N:12]=2)[CH2:6][CH2:5]1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:27][CH:25]([C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:13]2[N:12]=[C:11]([CH2:10][CH2:9][C:8]3[CH:35]=[CH:36][CH:37]=[CH:38][C:7]=3[C:4]3([C:1]([NH2:2])=[O:3])[CH2:6][CH2:5]3)[C:16]([CH3:17])=[CH:15][N:14]=2)=[CH:20][CH:21]=1)[CH3:26]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 86712321tert-Butyl (1-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-methylpyrimidin-2-yl)amino)phenyl)ethyl)carbamate

Product 1

HCID 732949461-(2-(2-(2-((4-(1-Aminoethyl)phenyl)amino)-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamideYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of tert-butyl (1-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-methylpyrimidin-2-yl)amino)phenyl)ethyl)carbamate A47 (0.110 g, 0.213 mmol) in DCM (10 mL) was treated with TFA (0.33 mL, 4.3 mmol) and stirred for 6 hours at room temperature. The volatiles were evaporated in vacuo before aq. NaOH (2 M, 30 mL) was added to the residue. The aqueous phase was extracted with EtOAc (3×30 mL) and the combined organics were washed with brine and dried over MgSO4. The solvent was removed in vacuo to give an off-white solid that still contained starting material. The solid was taken up in DCM (20 mL) and treated with TFA (0.17 mL, 2.2 mmol). The mixture was stirred at room temperature for 24 hours before the volatiles were removed in vacuo. Aq. NaOH (2 M, 30 mL) was added and the aqueous phase was extracted with EtOAc (3×30 mL). The organics were combined, washed with brine, dried (MgSO4) and the solvent removed in vacuo. The resultant white solid was dissolved in DCM and the desired product was precipitated by the addition of cyclohexane. The precipitate was isolated by vacuum filtration to give the title compound 50 (0.037 g, 42%) as a white solid. LCMS-A: rt 2.98 min; m/z 399 [M-NH2]+.

Workup

  1. customThe volatiles were evaporated in vacuo before aq. NaOH (2 M, 30 mL)
  2. additionwas added to the residue
  3. extractionThe aqueous phase was extracted with EtOAc (3×30 mL)
  4. washthe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed in vacuo
  7. customto give an off-white solid
  8. stirringThe mixture was stirred at room temperature for 24 hours before the volatiles
  9. customwere removed in vacuo
  10. additionAq. NaOH (2 M, 30 mL) was added
  11. extractionthe aqueous phase was extracted with EtOAc (3×30 mL)
  12. washwashed with brine
  13. dry with materialdried (MgSO4)
  14. customthe solvent removed in vacuo
  15. dissolutionThe resultant white solid was dissolved in DCM
  16. customthe desired product was precipitated by the addition of cyclohexane
  17. customThe precipitate was isolated by vacuum filtration

Sources & evidence

ORD record
ord-b3940e0ac1794e829ee1d9306ac8a492
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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