Cesium carbonate → HCID 86710360, compound

HRID 1398366Notes

Reaction equation

HRID 1398366 reaction equation
Cl[C:2]1[C:3]([CH:19]([F:21])[F:20])=[CH:4][C:5]2[C:14]3[C:9](=[C:10]([CH3:15])[N:11]=[CH:12][CH:13]=3)[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[CH:18]=1.[OH:22][CH2:23][C@@H:24]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:25][CH:26]([CH3:28])[CH3:27].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1>[F:20][CH:19]([F:21])[C:3]1[C:2]([O:22][CH2:23][C@@H:24]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[CH2:25][CH:26]([CH3:28])[CH3:27])=[CH:18][C:6]2[N:7]([CH3:17])[C:8](=[O:16])[C:9]3[C:14]([C:5]=2[CH:4]=1)=[CH:13][CH:12]=[N:11][C:10]=3[CH3:15]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 7018766Boc-L-leucinolHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 86710361HCID 86710361, compound

Product 1

HCID 86710360HCID 86710360, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 8-chloro-9-(difluoromethyl)-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (700 mg, 1.519 mmol), (S)-tert-butyl (1-hydroxy-4-methylpentan-2-yl)carbamate (660 mg, 3.04 mmol), 2-di-t-butylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (387 mg, 0.912 mmol), PdOAc2 (34.1 mg, 0.152 mmol) and Cs2CO3 (990 mg, 3.04 mmol) in toluene (20 mL) was heated at 80° C. for 16 h. After cooling to room temperature, the mixture was concentrated under reduced pressure. The residue was taken up in ethyl acetate and filtered through diatomaceous earth (Celite®). The organic layer was washed with brine and water; dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography using EtOAc-hexane as the eluent to afford (S)-tert-butyl (1-((9-(difluoromethyl)-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.6 g, 0.58 mmol, 54% yield) as a brown gummy solid. LC/MS (ESI) m/e 490.2 [(M+H)+, calcd for C26H34F2N3O4, 490.2]; LC/MS retention time (method B): tR=2.72 min.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. filtrationfiltered through diatomaceous earth (Celite®)
  3. washThe organic layer was washed with brine and water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-9c8c48cfb6684c368f951bab1fbdaf1d
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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