Monomethylamine methanol → Tert-butyl 3-((6-methoxy-2'-(methylamino)-[3,4'-bipyridin]-5-yl)amino)azetidine-1-carboxylate

HRID 2283468Notes

Reaction equation

HRID 2283468 reaction equation
F[C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][C:11]([O:26][CH3:27])=[C:12]([NH:14][CH:15]3[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]3)[CH:13]=2)[CH:5]=[CH:4][N:3]=1.[CH3:28][NH2:29].CO>CN1C(=O)CCC1>[CH3:27][O:26][C:11]1[N:10]=[CH:9][C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:29][CH3:28])[CH:7]=2)=[CH:13][C:12]=1[NH:14][CH:15]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1

Participants

4

Reactant 2

HCID 57454252Monomethylamine methanolHCID 118251462Tert-butyl 3-((2'-fluoro-6-methoxy-[3,4'-bipyridin]-5-yl)amino)azetidine-1-carboxylate

Product 1

HCID 118251491Tert-butyl 3-((6-methoxy-2'-(methylamino)-[3,4'-bipyridin]-5-yl)amino)azetidine-1-carboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of tert-butyl 3-((2′-fluoro-6-methoxy-[3,4′-bipyridin]-5-yl)amino)azetidine-1-carboxylate (530 mg, 1.42 mmol) in NMP (3 mL) was added CH3NH2/MeOH (5 mL). The reaction mixture was stirred while being heated at 140° C. in a microwave for 1 h. The mixture was cooled to rt, the solvent was removed and diluted with ethyl acetate (100 mL). The organic layer was washed with water (60 mL), brine (60 mL), dried over Na2SO4, filtered, concentrated in vacuo, and the residue was purified by flash chromatography to obtain 436 mg of tert-butyl 3-((6-methoxy-2′-(methylamino)-[3,4′-bipyridin]-5-yl)amino)azetidine-1-carboxylate as a yellow solid (80%): 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J=5.3 Hz, 1H), 7.72 (d, J=2.1 Hz, 1H), 6.63 (dd, J=5.3, 1.5 Hz, 1H), 6.58 (s, 1H), 6.39 (d, J=1.7 Hz, 1H), 4.63 (d, J=6.7 Hz, 1H), 4.53 (d, J=6.5 Hz, 1H), 4.27 (dd, J=8.8, 7.1 Hz, 2H), 4.18 (ddt, J=9.4, 7.0, 3.4 Hz, 1H), 3.97 (s, 3H), 3.74 (dd, J=9.0, 4.6 Hz, 2H), 2.90 (d, J=4.2 Hz, 3H), 1.37 (s, 9H); MS (ES) m/z 386 (M+H).

Workup

  1. temperatureThe mixture was cooled to rt
  2. customthe solvent was removed
  3. additiondiluted with ethyl acetate (100 mL)
  4. washThe organic layer was washed with water (60 mL), brine (60 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-d837b51e72e74b749c3389fae97938cb
Source dataset
uspto-grants-2015_09
Patent number
US09145393B2

Reaction notes

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