Trifluoroacetic acid → 2-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide

HRID 1473148Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1473148
FC(F)(F)C(O)=O.[NH2:8][C:9](=[O:49])[CH2:10][C:11]1[C:12]([CH2:17][CH2:18][C:19]2[C:24]([C:25]([F:28])([F:27])[F:26])=[CH:23][N:22]=[C:21]([NH:29][C:30]3[CH:35]=[CH:34][C:33]([CH:36]4[CH2:41][CH2:40][N:39](C(OC(C)(C)C)=O)[CH2:38][CH2:37]4)=[CH:32][CH:31]=3)[N:20]=2)=[N:13][CH:14]=[CH:15][CH:16]=1>C(Cl)Cl.C1CCCCC1>[NH:39]1[CH2:40][CH2:41][CH:36]([C:33]2[CH:34]=[CH:35][C:30]([NH:29][C:21]3[N:20]=[C:19]([CH2:18][CH2:17][C:12]4[C:11]([CH2:10][C:9]([NH2:8])=[O:49])=[CH:16][CH:15]=[CH:14][N:13]=4)[C:24]([C:25]([F:28])([F:26])[F:27])=[CH:23][N:22]=3)=[CH:31][CH:32]=2)[CH2:37][CH2:38]1

Komponenten

5

Edukt 2

HCID 6422Trifluoroacetic acidHCID 71209188tert-Butyl 4-(4-((4-(2-(3-(2-amino-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Produkt 1

HCID 601648082-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamideAusbeute 66,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittel2×HCID 8078CyclohexaneLösungsmittel

Versuchsvorschrift

Trifluoroacetic acid (0.337 mL, 4.40 mmol) was added to a solution tert-butyl 4-(4-((4-(2-(3-(2-amino-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I124) (64.3 mg, 0.110 mmol) in dry DCM (15 mL) under an atmosphere of nitrogen and the reaction was stirred at room temperature for 23 hours. The volatiles were removed in vacuo and the residue partitioned between EtOAc (40 mL) and 2 M NaOH (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic layers were washed with water (40 mL), brine (40 mL) and dried over Na2SO4. After filtration the solvent was removed under reduced pressure to give a yellow solid which was suspended in DCM (5 mL) and cyclohexane (15 mL). The precipitate was filtered to afford the title compound (32) (35.5 mg, 53%) as yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.05 (s, 1H), 8.64 (s, 1H), 8.36 (dd, J=4.8, 1.7 Hz, 1H), 7.62-7.55 (m, 3H), 7.53 (s, 1H), 7.18 (dd, J=7.6, 4.8 Hz, 1H), 7.15 (d, J=8.6 Hz, 2H), 7.00 (s, 1H), 3.53 (s, 2H), 3.24 (s, 4H), 3.02 (d, J=11.9 Hz, 2H), 2.61-2.52 (m, peaks obscured by solvent), 1.67 (d, J=11.3 Hz, 2H), 1.49 (qd, J=12.2, 3.8 Hz, 2H). LCMS Method C: rt 1.50, 1.59 min; m/z 485 [M+H]+.

Aufarbeitung

  1. customThe volatiles were removed in vacuo
  2. customthe residue partitioned between EtOAc (40 mL) and 2 M NaOH (50 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
  5. washThe combined organic layers were washed with water (40 mL), brine (40 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration the solvent
  8. customwas removed under reduced pressure
  9. customto give a yellow solid which
  10. filtrationThe precipitate was filtered

Quellen und Nachweise

ORD-Eintrag
ord-045427cf0b6e45cdb4504b62e482bcbe
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012461B2

Notizen zur Reaktion

Wird geladen…