Sodium Hydroxide → HCID 86710425, compound

HRID 1398446Notes

Reaction equation

HRID 1398446 reaction equation
I[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].N1CCC[C@H]1C(O)=O.[CH3:42][S:43]([OH:45])=[O:44].[Na].[OH-].[Na+]>CS(C)=O.[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]([CH3:31])([CH3:30])[CH3:32])[CH2:22][CH:23]([CH3:24])[CH3:25])[C:2]([S:43]([CH3:42])(=[O:45])=[O:44])=[CH:3][C:4]2=1

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 87251Methanesulfinic acidHCID 145742L-ProlineHCID 5360545SodiumHCID 86710426HCID 86710426, compound

Product 1

HCID 86710425HCID 86710425, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

(S)-tert-butyl (1-((9-iodo-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (100 mg, 0.177 mmol), L-proline (20.36 mg, 0.177 mmol), methanesulfinic acid, sodium salt (181 mg, 1.769 mmol), NaOH (11.32 mg, 0.283 mmol) and copper(I) iodide (33.7 mg, 0.177 mmol) were taken up in DMSO (5 mL) and purged with nitrogen gas for 5 min. The resultant mixture was sealed in a microwave tube and heated at 100° C. in a microwave for 2.5 h. The reaction mixture was cooled to room temperature, treated with ice-cold water (5 mL) and extracted with ethyl acetate (3×5 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford (S)-tert-butyl 1-(4,6-dimethyl-9-(methylsulfonyl)-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yloxy)-4-methylpentan-2-ylcarbamate (150 mg, 0.07 mmol, 39% crude yield, 24% purity) as a black gummy solid. The material was taken to the next step with out purification. LC/MS (ESI) m/e 518.2 [(M+H)+, calcd for C26H36N3O6S 518.2] LC/MS retention time (method B): tR=1.51 min.

Workup

  1. custompurged with nitrogen gas for 5 min
  2. customThe resultant mixture was sealed in a microwave tube
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiontreated with ice-cold water (5 mL)
  5. extractionextracted with ethyl acetate (3×5 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-01216e9392244c8ba3073ef9c2d3cae3
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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