Cesium carbonate → Tert-Butyl 4-(6-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-3-yl)-3-oxopiperazine-1-carboxylate

HRID 1772141Notes

Reaction equation

HRID 1772141 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.[NH2:11][C:12]1[N:17]=[CH:16][C:15]([N:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][C:19]2=[O:31])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Br:8][C:6]1[CH:7]=[C:2]([NH:11][C:12]2[N:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:20][C:19]3=[O:31])=[CH:14][CH:13]=2)[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 59290959Tert-butyl 4-(6-aminopyridin-3-yl)-3-oxopiperazine-1-carboxylate

Product 1

HCID 58043897Tert-Butyl 4-(6-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-3-yl)-3-oxopiperazine-1-carboxylateYield 84.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A 100-mL three-neck round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet and reflux condenser was charged with 3,5-dibromo-1-methylpyridin-2(1H)-one (530 mg, 1.99 mmol), 121b (580 mg, 1.99 mmol), cesium carbonate (1.43 g, 4.40 mmol) and 1,4-dioxane (30 mL). After bubbling nitrogen through the resulting mixture for 20 minutes, Xantphos (98.4 mg, 0.170 mmol) and tris(dibenzylideneacetone)dipalladium(0) (91.6 mg, 0.100 mmol) were added, and the reaction mixture was heated at reflux for 4 h. After this time, the reaction was cooled to room temperature, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography to afford an 84% yield (802 mg) of 121c as a yellow solid: mp 130-132° C.; 1H NMR (500 MHz, CDCl3) δ 8.68 (d, 1H, J=2.5 Hz), 8.24 (d, 1H, J=2.5 Hz), 7.98 (s, 1H), 7.52 (dd, 1H, J=9.0, 2.5 Hz), 7.00 (d, 1H, J=2.5 Hz), 6.82 (d, 1H, J=8.5 Hz), 4.26 (s, 2H), 3.81 (m, 2H), 3.73 (m, 2H), 3.60 (s, 3H), 1.50 (s, 9H); MS (ESI+) m/z 478.2 (M+H).

Workup

  1. customA 100-mL three-neck round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet
  2. temperaturereflux condenser
  3. customAfter bubbling nitrogen through the resulting mixture for 20 minutes
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 4 h
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-d62ea649299e4ddaa497bac54e7c7437
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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