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

HRID 1398375Notes

Reaction equation

HRID 1398375 reaction equation
Br[C:2]1[CH:3]=[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[C:18]=1[F:19].[OH:20][CH2:21][C:22]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:27])[CH2:23][CH:24]([CH3:26])[CH3:25].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>[F:19][C:18]1[C:6]2[N:7]([CH3:17])[C:8](=[O:16])[C:9]3[C:14]([C:5]=2[CH:4]=[CH:3][C:2]=1[O:20][CH2:21][C:22]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:34])[CH3:33])([CH3:27])[CH2:23][CH:24]([CH3:25])[CH3:26])=[CH:13][CH:12]=[N:11][C:10]=3[CH3:15]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 867103668-bromo-7-fluoro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-oneHCID 86710368tert-butyl N-(1-hydroxy-2,4-dimethylpentan-2-yl)carbamate

Product 1

HCID 86710367Tert-butyl (1-((7-fluoro-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-2,4-dimethylpentan-2-yl)carbamate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 8-bromo-7-fluoro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (350 mg, 1.090 mmol) and tert-butyl (1-hydroxy-2,4-dimethylpentan-2-yl)carbamate (504 mg, 2.180 mmol) in toluene (10 mL) was added cesium carbonate (355 mg, 1.09 mmol) and 2-Di-t-butylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (28 mg, 0.065 mmol). The reaction mixture was degassed with argon for 5 min and then palladium acetate (7.34 mg, 0.033 mmol) was added to it. The reaction mixture was heated to 100° C. for 18 h. Then, it was filtered through diatomaceous earth (Celite®) and the filtrate was evaporated to afford tert-butyl (1-((7-fluoro-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-2,4-dimethylpentan-2-yl)carbamate which was taken to next step without purification. LC/MS (ESI) m/e 472.2 [(M+H)+, calcd for C26H35FN3O4 472.2]; LC/MS retention time (method C): tR=2.17 min.

Workup

  1. customThe reaction mixture was degassed with argon for 5 min
  2. filtrationThen, it was filtered through diatomaceous earth (Celite®)
  3. customthe filtrate was evaporated

Sources & evidence

ORD record
ord-82775d9a1911472f95866b00a773d94c
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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