Trifluoroacetic acid → 2-(2-(2-(2-((2-Methoxy-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 705747Notes

Reaction equation

HRID 705747 reaction equation
[NH2:1][C:2](=[O:44])[CH2:3][C:4]1[CH:43]=[CH:42][CH:41]=[CH:40][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)=[CH:21][C:20]=2[O:38][CH3:39])[N:9]=1.C(O)(C(F)(F)F)=O>ClCCl>[CH3:39][O:38][C:20]1[CH:21]=[C:22]([CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH:23]=[CH:24][C:19]=1[NH:18][C:10]1[N:9]=[C:8]([CH2:7][CH2:6][C:5]2[CH:40]=[CH:41][CH:42]=[CH:43][C:4]=2[CH2:3][C:2]([NH2:1])=[O:44])[C:13]([C:14]([F:15])([F:16])[F:17])=[CH:12][N:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68283338tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidine-1-carboxylate

Product 1

HCID 601619862-(2-(2-(2-((2-Methoxy-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidine-1-carboxylate (I23) (2.694 g, 4.39 mmol) was dissolved in dichloromethane (150 mL), and TFA (15 mL) was added. The resulting mixture was stirred for 16 hours then concentrated. The residue was suspended in 10% sodium hydroxide (200 mL) then extracted with ethyl acetate (5×200 mL). The combined organic phases were washed with brine (300 mL), dried over sodium sulfate and evaporated to give the title compound (2) (2.252 g, 100% yield) as a white solid; 1H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 8.26 (d, J=8.3 Hz, 1H), 7.85 (s, 1H), 7.29-7.21 (m, overlaps with CHCl3), 6.87 (d, J=8.3 Hz, 1H), 6.80 (s, 1H), 5.43 (d, J=10.1 Hz, 2H), 3.92 (d, J=1.3 Hz, 3H), 3.70 (s, 2H), 3.20 (d, J=12.7 Hz, 2H), 3.15-3.05 (m, 4H), 2.75 (t, J=12.2 Hz, 2H), 2.61 (tt, J=12.0, 3.5 Hz, 1H), 1.89-1.76 (m, overlaps with water), 1.67 (qd, J=12.7, 3.9 Hz, 2H). LCMS Method C: rt 4.92 min; m/z 514.1 [M+H]+, 536.1 [M+Na]+; m/z 512.2 [M−H]−.

Workup

  1. concentrationthen concentrated
  2. extractionthen extracted with ethyl acetate (5×200 mL)
  3. washThe combined organic phases were washed with brine (300 mL)
  4. dry with materialdried over sodium sulfate
  5. customevaporated

Sources & evidence

ORD record
ord-a12acb94de644b098c33c4953de4ebef
Source dataset
uspto-grants-2015_11
Patent number
US09174946B2

Reaction notes

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