Trifluoroacetic acid → HCID 73054871, compound

HRID 1778966Notes

Reaction equation

HRID 1778966 reaction equation
[NH2:1][C:2](=[O:39])[CH2:3][C:4]1[CH:38]=[CH:37][CH:36]=[CH:35][C:5]=1[CH2:6][CH2:7][C:8]1[C:13]([CH3:14])=[CH:12][N:11]=[C:10]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[N:9]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.CO>[CH3:14][C:13]1[C:8]([CH2:7][CH2:6][C:5]2[CH:35]=[CH:36][CH:37]=[CH:38][C:4]=2[CH2:3][C:2]([NH2:1])=[O:39])=[N:9][C:10]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[CH:18][CH:17]=2)=[N:11][CH:12]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712637HCID 86712637, compound

Product 1

HCID 73054871HCID 73054871, compoundYield 35.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of tert-butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (A10) (28 mg, 0.053 mmol) in DCM (8 mL) was added TFA (2 mL) and the resulting solution was stirred at 25° C. for 24 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (10 mL) and 2 M NaOH (20 mL). The aqueous layer was extracted with EtOAc (2×10 mL) then the combined organic layers washed with brine (10 mL) and dried (MgSO4). The solvent was removed in vacuo to give a brown solid which was taken up in MeOH and purified by SCX cartridge (5 g, MeOH followed by 0.5 M NH3 in MeOH). The volatiles from the ammoniacal filtrate were removed in vacuo and the resulting solid residue suspended in cyclohexane and sonicated. The resulting suspension was filtered and the filter cake dried to give the title compound 2 as a light brown solid (8 mg, 35%); 1H NMR (400 MHz, d6-DMSO) δ 9.08 (s, 1H), 8.11 (s, 1H), 7.60 (dd, J=9.2, 2.2 Hz, 2H), 7.41 (s, 1H), 7.26-7.20 (m, 1H), 7.19-7.13 (m, 3H), 6.92 (s, 1H), 6.85 (d, J=9.1 Hz, 2H), 4.02 (s, 1H), 3.50 (s, 2H), 3.03 (dd, J=10.1, 5.7 Hz, 2H), 2.97 (m, 2H), 2.85 (m, 4H), 2.69-2.64 (m, 2H), 2.36-2.30 (m, 2H), 2.05 (s, 3H). LCMS-A: rt 4.364 min; m/z 431.1 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue was partitioned between EtOAc (10 mL) and 2 M NaOH (20 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  4. washthe combined organic layers washed with brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. customThe solvent was removed in vacuo
  7. customto give a brown solid which
  8. custompurified by SCX cartridge (5 g, MeOH followed by 0.5 M NH3 in MeOH)
  9. customThe volatiles from the ammoniacal filtrate were removed in vacuo
  10. customsonicated
  11. filtrationThe resulting suspension was filtered
  12. customthe filter cake dried

Sources & evidence

ORD record
ord-ccc1768f2fc54206ae893dc500bd0332
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

Loading…