Pyrazole → HCID 86710421, compound

HRID 1398440Notes

Reaction equation

HRID 1398440 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].[NH:34]1[CH:38]=[CH:37][CH:36]=[N:35]1.CNCCNC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CN(C=O)C.[Cu]I>[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]([CH3:32])([CH3:31])[CH3:30])[CH2:22][CH:23]([CH3:24])[CH3:25])[C:2]([N:34]3[CH:38]=[CH:37][CH:36]=[N:35]3)=[CH:3][C:4]2=1

Participants

8

Reactant 4

HCID 1048PyrazoleHCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 86710370HCID 86710370, compound

Product 1

HCID 86710421HCID 86710421, compoundYield 29.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
170 °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 (50 mg, 0.096 mmol) and 1H-pyrazole (7.88 mg, 0.116 mmol) in 1,4-dioxane (2 mL) and DMF (0.5 mL), was added copper(I) iodide (18.37 mg, 0.096 mmol), N1,N2-dimethylethane-1,2-diamine (17.00 mg, 0.193 mmol) and potassium phosphate (61.4 mg, 0.289 mmol). The reaction mixture was degassed with nitrogen for 5 min and heated to 170° C. for 1 h in a microwave. The reaction mixture was cooled to room temperature, filtered through diatomaceous earth (Celite®) and the filtrate concentrated under reduced pressure. The residue was purified by preparative TLC (eluent 2% MeOH:DCM) to afford (S)-tert-butyl 1-(4,6-dimethyl-5-oxo-9-(1H-pyrazol-1-yl)-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yloxy)-4-methylpentan-2-ylcarbamate (40 mg, 0.028 mmol, 29% yield) as a brown solid. LC/MS (ESI) m/e 406.5 [(M+H)+, calcd for C23H28N5O2 406.2] LC/MS retention time (method E): tR=0.71 min.

Workup

  1. customThe reaction mixture was degassed with nitrogen for 5 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered through diatomaceous earth (Celite®)
  4. concentrationthe filtrate concentrated under reduced pressure
  5. customThe residue was purified by preparative TLC (eluent 2% MeOH:DCM)

Sources & evidence

ORD record
ord-f930fc33c7494f3baa79dd85046b956a
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

Loading…