Cesium carbonate → (S)-tert-butyl (1-((2,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

HRID 1398428Notes

Reaction equation

HRID 1398428 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[CH:10][N:11]=[C:12]([CH3:15])[CH:13]=3)[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[CH:18]=1.[OH:19][CH2:20][C:21]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])(C)[CH2:22][CH:23]([CH3:25])[CH3:24].C(=O)([O-])[O-].[Cs+].[Cs+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:15][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][N:11]=1)[C:8](=[O:16])[N:7]([CH3:17])[C:6]1[CH:18]=[C:2]([O:19][CH2:20][C@@H:21]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:33])[CH3:32])[CH2:22][CH:23]([CH3:25])[CH3:24])[CH:3]=[CH:4][C:5]2=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 86710368tert-butyl N-(1-hydroxy-2,4-dimethylpentan-2-yl)carbamateHCID 867104148-chloro-2,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one

Product 1

HCID 86710415(S)-tert-butyl (1-((2,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamateYield 44.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To the stirred solution of 8-chloro-2,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (100 mg, 0.387 mmol) and tert-butyl (1-hydroxy-2,4-dimethylpentan-2-yl)carbamate (168 mg, 0.773 mmol) in toluene (5 mL) was added cesium carbonate (189 mg, 0.580 mmol) and 2-di-t-butylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (9.85 mg, 0.023 mmol). The reaction mixture was degassed with argon for 5 minutes and palladium(II) acetate (26 mg, 0.116 mmol) was added. The reaction mixture was heated to 100° C. for 18 h. The reaction mixture was filtered through diatomaceous earth (Celite®) and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography using ethyl acetate-petroleum ether to afford (S)-tert-butyl (1-((2,6-dimethyl-5-oxo-5,6 dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (100 mg, 0.171 mmol, 44% yield) as a dark yellow semi-solid. LC/MS (ESI) m/e 440.6 [(M+H+)+, calcd for C25H34N3O4 440.2]; LC/MS retention time (method D): tR=0.89 min.

Workup

  1. customThe reaction mixture was degassed with argon for 5 minutes
  2. filtrationThe reaction mixture was filtered through diatomaceous earth (Celite®)
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-09d92468721b414db294b102da3ccc68
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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