Trifluoroacetic acid → HCID 68282576, compound

HRID 1473162Notes

Reaction equation

HRID 1473162 reaction equation
[NH2:1][C:2](=[O:41])[CH2:3][C:4]1[CH:40]=[CH:39][CH:38]=[CH:37][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:24]=[CH:23][C:22]([CH:25]3[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26]3)=[CH:21][CH:20]=2)[N:9]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.C1CCCCC1>[NH:27]1[CH2:28][CH2:29][CH:25]([C:22]2[CH:23]=[CH:24][C:19]([NH:18][C:10]3[N:9]=[C:8]([CH2:7][CH2:6][C:5]4[CH:37]=[CH:38][CH:39]=[CH:40][C:4]=4[CH2:3][C:2]([NH2:1])=[O:41])[C:13]([C:14]([F:17])([F:15])[F:16])=[CH:12][N:11]=3)=[CH:20][CH:21]=2)[CH2:26]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71209140HCID 71209140, compound

Product 1

HCID 68282576HCID 68282576, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8078CyclohexaneSolvent

Procedure

To a solution of tert-butyl 3-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)pyrrolidine-1-carboxylate (I141) in DCM (20 mL) was added TFA (4.0 mL) and the reaction mixture was stirred at room temperature for 30 minutes. The solvent was removed in vacuo and the residue taken up in EtOAc (10 mL) and 2 M NaOH (10 mL). The organic layer was extracted with EtOAc (2×10 mL), and the combined layers washed with water (10 mL), brine (10 mL) and dried over MgSO4. The solvent was removed in vacuo to give a yellow solid. The solid was suspended in cyclohexane and filtered to give a brown solid (42 mg). The product was purified further by RP-HPLC (Waters, 0-80% CH3CN in H2O over 20 minutes at a flow rate of 10 mL/min). Fractions containing product were basified (pH 10) with 2 M NaOH and extracted with EtOAc. The combined organic layers were washed with brine (10 mL), dried (MgSO4) and the solvent removed in vacuo to give the title compound (35) (17 mg, 27%) as a brown oil; 1H-NMR (400 MHz, d4-MeOD) δ 8.56 (d, J=0.6 Hz, 1H), 7.73-7.68 (m, 2H), 7.33-7.16 (m, 6H), 3.67 (s, 2H), 3.60-3.46 (m, 2H), 3.42-3.33 (m, 2H), 3.14 (m, 5H), 2.45 (dtd, J=10.1, 7.1, 3.4 Hz, 1H), 2.18-2.05 (m, 1H); LCMS Method C: rt 4.84 min; m/z 470.1 [M+H]+.

Workup

  1. customThe solvent was removed in vacuo
  2. extractionThe organic layer was extracted with EtOAc (2×10 mL)
  3. washthe combined layers washed with water (10 mL), brine (10 mL)
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed in vacuo
  6. customto give a yellow solid
  7. filtrationfiltered

Sources & evidence

ORD record
ord-494abe35874b41adb55dcaf56a1bde70
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

Loading…