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 2208817Notes

Reaction equation

HRID 2208817 reaction equation
[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

Participants

4

Reactant 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

Product 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]benzamideYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-7567220263f64887b1e449a4be19de37
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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