Triethylamine → HCID 68748188, compound

HRID 1047160Notes

Reaction equation

HRID 1047160 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([C@H:12]1[CH2:17][CH2:16][CH2:15][N:14]([CH2:18][CH2:19][N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])[CH2:13]1)[CH:7]=[C:6]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:5]2=[O:30].CC1(C)C(C)(C)[O:35][B:34](B2OC(C)(C)C(C)(C)O2)[O:33]1.C(N(CC)CC)C.C([O-])(=O)C.[K+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:21]([N:20]([CH2:23][CH3:24])[CH2:19][CH2:18][N:14]1[CH2:15][CH2:16][CH2:17][CH:12]([N:8]2[C:9]3[N:10]=[CH:11][C:2]([B:34]([OH:35])[OH:33])=[CH:3][C:4]=3[C:5](=[O:30])[C:6]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:7]2)[CH2:13]1)[CH3:22]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 69621278HCID 69621278, compound2×

Product 1

HCID 68748188HCID 68748188, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

(S)-ethyl 6-bromo-1-(1-(2-(diethylamino)ethyl)piperidin-3-yl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 35, 2.7 g, 5.63 mmol) and PdCl2(PPh3)2 (0.395 g, 0.56 mmol) were combined and suspended in 1,4-dioxane (50 mL). The slurry was degassed, purged with nitrogen and then gently warmed to 75° C. for 20 min. 4,4,4′,4′,5,5,5′,5′-Octamethyl-2,2′-bi(1,3,2-dioxaborolane) (4.29 g, 16.90 mmol) was then added in a single portion and the temperature was raised to 100° C. After an hour of heating, triethylamine (0.784 mL, 5.63 mmol) and potassium acetate (1.658 g, 16.90 mmol) were added sequentially. The reaction mixture was stirred at reflux overnight. The reaction mixture was cooled to room temperature and filtered through a celite. Solvent was removed in vacuo and the residue was purified via ISCO DCM/Methanol 0-20% gradient. (S)-8-(1-(2-(diethylamino)ethyl)piperidin-3-yl)-6-(ethoxycarbonyl)-5-oxo-5,8-dihydro-1,8-naphthyridin-3-ylboronic acid (2.0 g, 80%) was recovered as a brown solid.

Workup

  1. customThe slurry was degassed
  2. custompurged with nitrogen
  3. temperaturethe temperature was raised to 100° C
  4. temperatureAfter an hour of heating
  5. temperatureat reflux overnight
  6. temperatureThe reaction mixture was cooled to room temperature
  7. filtrationfiltered through a celite
  8. customSolvent was removed in vacuo
  9. customthe residue was purified via ISCO DCM/Methanol 0-20% gradient
  10. custom(S)-8-(1-(2-(diethylamino)ethyl)piperidin-3-yl)-6-(ethoxycarbonyl)-5-oxo-5,8-dihydro-1,8-naphthyridin-3-ylboronic acid (2.0 g, 80%) was recovered as a brown solid

Sources & evidence

ORD record
ord-1c8592438e3e460288efcebdc804a40a
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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