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Trifluoroacetic acid → 5-(azetidin-3-yl)-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2-methyl-3-[methyl(oxan-4-yl)amino]benzamide

HRID 2208817
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2208817
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[CH:15]=[C:16]([CH:29]2[CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30]2)[CH:17]=[C:18]([N:21]([CH3:28])[CH:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:19]=1[CH3:20])=[O:13].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:31]1[CH2:30][CH:29]([C:16]2[CH:17]=[C:18]([N:21]([CH3:28])[CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[C:19]([CH3:20])=[C:14]([CH:15]=2)[C:12]([NH:11][CH2:10][C:3]2[C:4](=[O:9])[NH:5][C:6]([CH3:8])=[CH:7][C:2]=2[CH3:1])=[O:13])[CH2:32]1
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Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acidHCID 70913254Tert-butyl 3-(3-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]carbamoyl}-4-methyl-5-[methyl(oxan-4-yl)amino]phenyl)azetidine-1-carboxylate

Produkt 1

HCID 708737555-(azetidin-3-yl)-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2-methyl-3-[methyl(oxan-4-yl)amino]benzamideAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344
Dichloromethane
Lösungsmittel

Versuchsvorschrift

To a stirred solution of tert-butyl 3-(3-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]carbamoyl}-4-methyl-5-[methyl(oxan-4-yl)amino]phenyl)azetidine-1-carboxylate (29 mg, 1.29 mmol) in DCM (4 ml) was added TFA (1 ml) and the solution was stirred at room temperature for 90 min after which the solvent was evaporated and saturated aqueous NaHCO3 was added until pH7-8. The aqueous phase was extracted with a 1:1 mixture IPA:CHCl3 (2×50 ml), and the combined organic phases washed with brine (30 ml, dried with Na2SO4, filtered and evaporated. The residue was purified by preparative HPLC to afford the title compound as a white solid (15 mg, 42%). LC-MS 100%, m/z=439.3, 1H NMR (500 MHz, MeOD) δ 7.19 (d, J=1.4 Hz, 1H), 7.10 (d, J=1.5 Hz, 1H), 6.12 (s, 1H), 4.46 (s, 2H), 4.41-4.27 (m, 2H), 4.26-4.13 (m, 3H), 3.93 (d, J=11.4 Hz, 2H), 3.36 (td, J=11.3, 3.3 Hz, 2H), 3.06 (dq, J=14.6, 5.0 Hz, 1H), 2.65 (s, 3H), 2.39 (s, 3H), 2.26 (s, 3H), 2.24 (s, 3H), 1.75-1.60 (m, 4H).

Aufarbeitung

  1. customwas evaporated
  2. additionsaturated aqueous NaHCO3 was added until pH7-8
  3. extractionThe aqueous phase was extracted with a 1:1 mixture IPA
  4. washCHCl3 (2×50 ml), and the combined organic phases washed with brine (30 ml
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-7567220263f64887b1e449a4be19de37
Quelldatensatz
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09376422B2

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