Lithium Chloride → HCID 86710429, compound

HRID 1398449Notes

Reaction equation

HRID 1398449 reaction equation
Br[C:2]1[S:6][CH:5]=[N:4][CH:3]=1.Br[C:8]1[C:24]([O:25][CH2:26][C@@H:27]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH2:28][CH:29]([CH3:31])[CH3:30])=[CH:23][C:11]2[N:12]([CH3:22])[C:13](=[O:21])[C:14]3[C:19]([C:10]=2[CH:9]=1)=[CH:18][CH:17]=[N:16][C:15]=3[CH3:20].[Cl-].[Li+]>O1CCOCC1>[CH3:20][C:15]1[N:16]=[CH:17][CH:18]=[C:19]2[C:14]=1[C:13](=[O:21])[N:12]([CH3:22])[C:11]1[CH:23]=[C:24]([O:25][CH2:26][C@@H:27]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:36])([CH3:38])[CH3:37])[CH2:28][CH:29]([CH3:31])[CH3:30])[C:8]([C:2]3[S:6][CH:5]=[N:4][CH:3]=3)=[CH:9][C:10]2=1

Participants

5

Reactant 3

HCID 433294Lithium ChlorideHCID 5460595-BromothiazoleHCID 86710370HCID 86710370, compound

Product 1

HCID 86710429HCID 86710429, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

5-Bromothiazole (0.050 g, 0.305 mmol) and hexamethyltin (0.158 mL, 0.762 mmol) were taken up in 1,4-dioxane (1 mL) and purged with nitrogen for 10 min. Tetrakis (triphenylphosphine)palladium (0.035 g, 0.030 mmol) was added and the reaction mixture was stirred for 2 h at rt. (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 (0.158 g, 0.305 mmol) and lithium chloride (0.013 g, 0.305 mmol) were added and the mixture was purged with N2 for 10 min. The reaction mixture was then heated for 16 h at 90° C. After cooling, the reaction mixture was filtered through diatomaceous earth (Celite®) and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford (S)-tert-butyl 1-(4,6-dimethyl-5-oxo-9-(thiazol-5-yl)-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yloxy)-4-methylpentan-2-ylcarbamate (40 mg, 0.053 mmol, 18% yield) as a yellow solid. LC/MS (ESI) m/e 23.6 [(M+H)+, calcd for C28H35N4O4S 523.2]; LC/MS retention time (method E): tR=1.09 min.

Workup

  1. custompurged with nitrogen for 10 min
  2. customthe mixture was purged with N2 for 10 min
  3. temperatureThe reaction mixture was then heated for 16 h at 90° C
  4. temperatureAfter cooling
  5. filtrationthe reaction mixture was filtered through diatomaceous earth (Celite®)
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-650dc92ca01d40c9bd0eb2a97f28be28
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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