Cesium carbonate → HCID 86710331, compound

HRID 1398327Notes

Reaction equation

HRID 1398327 reaction equation
Cl[C:2]1[C:3]([F:18])=[CH:4][C:5]2[C:14]3[C:9](=[CH:10][N:11]=[CH:12][CH:13]=3)[C:8](=[O:15])[N:7]([CH3:16])[C:6]=2[CH:17]=1.[OH: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].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:18][C:3]1[C:2]([O:19][CH2:20][C@@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:30])([CH3:32])[CH3:31])[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:17][C:6]2[N:7]([CH3:16])[C:8](=[O:15])[C:9]3[C:14]([C:5]=2[CH:4]=1)=[CH:13][CH:12]=[N:11][CH:10]=3

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 7018766Boc-L-leucinolHCID 86710330HCID 86710330, compound

Product 1

HCID 86710331HCID 86710331, compoundYield 15.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred suspension of 8-chloro-9-fluoro-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (40 mg, 0.152 mmol), (S)-tert-butyl (1-hydroxy-4-methylpentan-2-yl)carbamate (39.7 mg, 0.183 mmol), di-tert-butyl(2′,4′,6′-triisopropyl-[1′,1′-biphenyl]-2-yl)phosphine (38.8 mg, 0.091 mmol) and cesium carbonate (74.4 mg, 0.228 mmol) in toluene (4 mL) was added palladium(II)acetate (10.26 mg, 0.046 mmol). Nitrogen gas was bubbled through the mixture for 5 min, and then the reaction mixture was heated to 85° C. for 8 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (2 mL) and filtered through diatomaceous earth (Celite®). The filtrate was washed with water (2×2 mL) and brine (2×2 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (60% ethyl acetate in hexanes) to afford (S)-tert-butyl (1-((9-fluoro-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (28 mg, 0.023 mmol, 15% yield). LC/MS (ESI) m/e 444.2 [(M+H)+, calcd for C24H31lFN3O4 444.2]; LC/MS retention time (method A): tR=2.02 min.

Workup

  1. customNitrogen gas was bubbled through the mixture for 5 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with ethyl acetate (2 mL)
  4. filtrationfiltered through diatomaceous earth (Celite®)
  5. washThe filtrate was washed with water (2×2 mL) and brine (2×2 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified via silica gel column chromatography (60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-6064124ae53f4282ad5491f3addf157e
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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