Acetic Acid → (S)-2-(1-((4,6-dimethyl-5-oxo 5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione

HRID 1398445Notes

Reaction equation

HRID 1398445 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([CH3:13])[C:8]1[CH:14]=[C:15]([O:18][CH2:19][C@@H:20]([NH:25][C:26](=O)[O:27]C(C)(C)C)[CH2:21][CH:22]([CH3:24])[CH3:23])[CH:16]=[CH:17][C:7]2=1.I(O)(=O)(=O)=O.OS(O)(=O)=O.II.[CH3:45][C:46]([OH:48])=O>>[CH3:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([CH3:13])[C:8]1[CH:14]=[C:15]([O:18][CH2:19][C@@H:20]([N:25]3[C:46](=[O:48])[C:45]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[C:26]3=[O:27])[CH2:21][CH:22]([CH3:24])[CH3:23])[CH:16]=[CH:17][C:7]2=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 807IodineHCID 1118Sulfuric AcidHCID 65185Metaperiodic acidHCID 86710338(S)-tert-butyl (1-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 86710374(S)-2-(1-((4,6-dimethyl-5-oxo 5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione

Conditions

Temperature
80 °C

Procedure

(S)-tert-Butyl (1-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (300 mg, 0.683 mmol) was taken up in AcOH (15 mL) and treated with periodic acid (156 mg, 0.683 mmol), and H2SO4 (0.018 mL, 0.341 mmol). The reaction mixture was heated to 80° C. and maintained for 20 min after which iodine (104 mg, 0.410 mmol) was added and heating was continued at 80° C. for an additional 3 h. After cooling, the volatiles were evaporated and the residue was taken up in with ethyl acetate (25 mL). The organic layer was washed with saturated aqueous NaHCO3 (10 mL), then brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford (S)-2-(1-(4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yloxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (300 mg, 0.61 mmol, 90% crude yield) as a brown solid. The material was taken to the next step without further purification. LC/MS (ESI) m/e 466.1 [(M+H)+, calcd for C20H25IN3O2 466.1] LC/MS retention time (method D): tR=0.58 min.

Workup

  1. additionwas added
  2. temperatureheating
  3. temperatureAfter cooling
  4. customthe volatiles were evaporated
  5. washThe organic layer was washed with saturated aqueous NaHCO3 (10 mL)
  6. dry with materialbrine (10 mL), dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1760ca0c2eea4be990e85ea3981b1c92
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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