Trifluoroacetic acid → HCID 60162121, compound

HRID 705757Notes

Reaction equation

HRID 705757 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH:41]=[CH:42][CH:43]=1)[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]([CH:26]3[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]3)=[CH:22][C:21]=2[O:39][CH3:40])[N:10]=1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O>C1COCC1>[CH3:40][O:39][C:21]1[CH:22]=[C:23]([CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH:24]=[CH:25][C:20]=1[NH:19][C:11]1[N:10]=[C:9]([CH2:8][CH2:7][C:6]2[CH:5]=[C:4]([CH:43]=[CH:42][CH:41]=2)[C:1]([NH2:2])=[O:3])[C:14]([C:15]([F:16])([F:17])[F:18])=[CH:13][N:12]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68283219Tert-butyl 4-(4-((4-(3-carbamoylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidine-1-carboxylate

Product 1

HCID 60162121HCID 60162121, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of tert-butyl 4-(4-((4-(3-carbamoylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidine-1-carboxylate, (I36) (0.070 g, 0.12 mmol) and TFA (0.200 mL, 2.61 mmol) in THF (3 mL) was stirred 16 hours at room temperature. The mixture was concentrated under reduced pressure and azeotroped with toluene. The residue was then purified using a SCX cartridge (MeOH, 0.5% NH3/MeOH). The methanolic ammonia eluent was concentrated then dissolved in hot acetonitrile which was allowed to cool to room temperature. The cooled acetonitrile solution was filtered and the filtrate was concentrated, taken up in hot acetonitrile (2 mL) and water (1 mL) then freeze dried to give the title compound (5) (49.4 mg, 85%) as a white solid. A portion of this material was further purified by mass directed auto preparative HPLC to give the title compound (5) (4.5 mg) as a while solid; 1H NMR (400 MHz, d6-DMSO) δ 8.90 (m, 1H), 8.57 (s, 1H), 8.41 (s, 1H), 7.93 (s, 1H), 7.77 (s, 1H), 7.71 (m, 1H), 7.62 (dd, J=7.5, 7.5 Hz, 1H), 7.34 (m, 2H), 6.94 (dd, J=7.3, 1.6 Hz, 1H), 6.82 (ddd, J=7.9, 3.4, 1.5 Hz, 1H), 3.82 (s, 3H), 3.12 (m, 2H), 3.05 (m, 4H), 2.89 (m, 1H), 2.68 (m, 2H), 2.20 (m, 1H), 1.78 (m, 2H), 1.64 (m, 2H). LCMS Method C: rt 4.89 min; m/z 500.1 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customazeotroped with toluene
  3. customThe residue was then purified
  4. concentrationThe methanolic ammonia eluent was concentrated
  5. dissolutionthen dissolved in hot acetonitrile which
  6. temperatureto cool to room temperature
  7. filtrationThe cooled acetonitrile solution was filtered
  8. concentrationthe filtrate was concentrated
  9. dry with materialwater (1 mL) then freeze dried

Sources & evidence

ORD record
ord-3dc077c197ec4fc899eb2a938d5dcf80
Source dataset
uspto-grants-2015_11
Patent number
US09174946B2

Reaction notes

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