Pyridine → HCID 86710379, compound

HRID 1398392Notes

Reaction equation

HRID 1398392 reaction equation
Br[C:2]1[C:18]([O:19][CH2:20][C@@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:17][C:5]2[N:6]([CH3:16])[C:7](=[O:15])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][C:9]=3[CH3:14].C(=O)([O-])[O-].[Na+].[Na+].[CH:40](B1OB(C=C)OB(C=C)O1)=[CH2:41].N1C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C.O.C1(C)C=CC=CC=1>[CH3:14][C:9]1[N:10]=[CH:11][CH:12]=[C:13]2[C:8]=1[C:7](=[O:15])[N:6]([CH3:16])[C:5]1[CH:17]=[C:18]([O:19][CH2:20][C@@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:22][CH:23]([CH3:24])[CH3:25])[C:2]([CH:40]=[CH2:41])=[CH:3][C:4]2=1

Participants

9

Reactant 4

HCID 1049PyridineHCID 10340Sodium CarbonateHCID 2734807TrivinylboroxinHCID 86710370HCID 86710370, compound

Product 1

HCID 86710379HCID 86710379, compoundYield 19%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To the solution of (S)-tert-butyl (1-((9-bromo-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (300 mg, 0.579 mmol), prepared as described in Example 3, Part A, in the solvent mixture toluene (10 mL), water (0.5 mL) and ethanol (2 mL) was added sodium carbonate (184 mg, 1.736 mmol), tetrakis(triphenylphosphine)palladium (33.4 mg, 0.029 mmol) and 2,4,6-trivinyl-1,3,5,2,4,6-trioxatriborinane with pyridine (1:1) (167 mg, 0.694 mmol). The reaction mixture was degassed for 30 min. Then the reaction mixture was allowed to stir at 90° C. for 16 h. After cooling to room temperature the mixture was filtered through diatomaceous earth (Celite®) eluting with EtOAc. The filtrate was concentrated under reduced pressure. The residue was taken up in EtOAc and water. The solution was extracted with ethyl acetate (2×15 mL). The combined organic layers were washed with water (10 mL), brine (10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (60% Ethyl acetate in hexane) to afford (S)-tert-butyl (1-((4,6-dimethyl-5-oxo-9-vinyl-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (300 mg, 0.110 mmol, 19% yield) as a pale yellow semi solid. LC/MS, (ESI) m/z 466.5 [(M+H)+, calcd for C27H36N3O4 466.3]; LC/MS retention time (method E): tR=1.18 min.

Workup

  1. customThe reaction mixture was degassed for 30 min
  2. temperatureAfter cooling to room temperature the mixture
  3. filtrationwas filtered through diatomaceous earth (Celite®)
  4. washeluting with EtOAc
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. extractionThe solution was extracted with ethyl acetate (2×15 mL)
  7. washThe combined organic layers were washed with water (10 mL), brine (10 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (60% Ethyl acetate in hexane)

Sources & evidence

ORD record
ord-ba3fec30a35e42af9baa6a9bc44d6249
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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