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

HRID 1473110Notes

Reaction equation

HRID 1473110 reaction equation
[NH2:1][C:2](=[O:42])[CH2:3][C:4]1[CH:41]=[CH:40][CH:39]=[CH:38][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[O:30][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>[NH:27]1[CH2:28][CH2:29][O:30][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:38]=[CH:39][CH:40]=[CH:41][C:4]=4[CH2:3][C:2]([NH2:1])=[O:42])[C:13]([C:14]([F:17])([F:15])[F:16])=[CH:12][N:11]=3)=[CH:20][CH:21]=2)[CH2:26]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86675724tert-Butyl 2-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)morpholine-4-carboxylate

Product 1

HCID 601647002-(2-(2-((4-(Morpholin-2-yl)phenyl)-amino)-5-(trifluoromethyl)pyrimidin-4-yl-ethyl)phenyl)acetamideYield 89.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 2-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)morpholine-4-carboxylate (I91) (23 mg, 0.039 mmol) was stirred with DCM (3 mL) and TFA (0.3 mL). After 18 hours the mixture was concentrated and the residue suspended in 10% aqueous NaOH (1 mL) and brine (1 mL). The mixture was extracted with ethyl acetate (5×3 mL), and the combined ethyl acetate phases washed with brine (20 mL), dried over sodium sulfate and evaporated to give the title compound (22) (17 mg, 89%) as a white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.19 (s, 1H), 8.67 (s, 1H), 7.74-7.67 (m, 2H), 7.42 (s, 1H), 7.27 (d, J=8.6 Hz, 2H), 7.25-7.21 (m, 1H), 7.19-7.14 (m, 3H), 6.91 (s, 1H), 4.32 (dd, J=10.1, 2.1 Hz, 1H), 3.86 (d, J=10.9 Hz, 1H), 3.58 (dt, J=11.2, 7.2 Hz, 1H), 3.50 (s, 2H), 3.15-2.98 (m, 4H), 2.89 (dd, J=12.3, 2.2 Hz, 1H), 2.72 (d, J=5.2 Hz, 2H). LCMS Method C: rt 4.75 min; m/z 486.1 [M+H]+, 508.0 [M+Na]+; m/z 484.1 [M−H]−.

Workup

  1. concentrationAfter 18 hours the mixture was concentrated
  2. extractionThe mixture was extracted with ethyl acetate (5×3 mL)
  3. washthe combined ethyl acetate phases washed with brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. customevaporated

Sources & evidence

ORD record
ord-8add0254d3eb4179a737e6f6aa86e10b
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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