Trifluoroacetic acid → HCID 73055150, compound

HRID 1778988Notes

Reaction equation

HRID 1778988 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:24]=[CH:23][C:22]([CH:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]3)=[C:21]([F:38])[CH:20]=2)[N:9]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.C(Cl)Cl.C1CCCCC1>[F:38][C:21]1[CH:20]=[C:19]([NH:18][C:10]2[N:9]=[C:8]([CH2:7][CH2:6][C:5]3[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=3[CH2:3][C:2]([NH2:1])=[O:43])[C:13]([C:14]([F:17])([F:15])[F:16])=[CH:12][N:11]=2)[CH:24]=[CH:23][C:22]=1[CH:25]1[CH2:26][CH2:27][NH:28][CH2:29][CH2:30]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712651HCID 86712651, compound

Product 1

HCID 73055150HCID 73055150, compoundYield 61.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21916607Dichloromethane cyclohexaneSolvent

Procedure

To a solution of tert-butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-fluorophenyl)piperidine-1-carboxylate (A32) (0.209 g, 0.347 mmol) in DCM (4 mL) was added TFA (1.0 mL) and the resulting mixture was stirred at room temperature for 16 hours. The volatiles were removed in vacuo and the residue partitioned between EtOAc (10 mL) and 2 M aqueous NaOH (10 mL). The aqueous layer was extracted with EtOAc (2×10 mL) then the combined organic layers washed with water (10 mL), brine (10 mL) and dried over MgSO4. The volatiles were removed in vacuo to give a yellow solid which was suspended in DCM/cyclohexane and the resulting suspension filtered to give the title compound 7 as a white solid (0.107 g, 61%); 1H NMR (400 MHz, d4-MeOH) δ 8.59 (s, 1H), 7.66 (dd, J=13.2, 2.1 Hz, 1H), 7.39 (dd, J=8.5, 2.1 Hz, 1H), 7.28-7.15 (m, 5H), 3.68 (s, 2H), 3.23-3.14 (m, 4H), 3.10 (dd, J=10.6, 5.4 Hz, 2H), 2.99 (tt, J=11.7, 3.8 Hz, 1H), 2.80 (td, J=12.4, 2.9 Hz, 2H), 1.87-1.68 (m, 4H). LCMS-A: rt 4.851 min; m/z 502.2 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue partitioned between EtOAc (10 mL) and 2 M aqueous NaOH (10 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  4. washthe combined organic layers washed with water (10 mL), brine (10 mL)
  5. dry with materialdried over MgSO4
  6. customThe volatiles were removed in vacuo
  7. customto give a yellow solid which
  8. filtrationthe resulting suspension filtered

Sources & evidence

ORD record
ord-74fc07cdbaef413aabd8b552291e4c16
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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