Phthalic Anhydride → HCID 86710422, compound

HRID 1398442Notes

Reaction equation

HRID 1398442 reaction equation
[NH2:1][C@@H:2]([CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:3][O:4][C:5]1[C:6]([I:22])=[CH:7][C:8]2[C:17]3[C:12](=[C:13]([CH3:18])[N:14]=[CH:15][CH:16]=3)[C:11](=[O:19])[N:10]([CH3:20])[C:9]=2[CH:21]=1.C(N(C(C)C)C(C)C)C.[C:36]1(=O)[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38](=[O:45])[O:37]1>O1CCOCC1.CCOC(C)=O.C(Cl)Cl>[I:22][C:6]1[C:5]([O:4][CH2:3][C@@H:2]([N:1]2[C:36](=[O:37])[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:38]2=[O:45])[CH2:23][CH:24]([CH3:26])[CH3:25])=[CH:21][C:9]2[N:10]([CH3:20])[C:11](=[O:19])[C:12]3[C:17]([C:8]=2[CH:7]=1)=[CH:16][CH:15]=[N:14][C:13]=3[CH3:18]

Participants

7

Reactant 3

HCID 6811Phthalic AnhydrideHCID 81531DiisopropylethylamineHCID 86710423HCID 86710423, compound

Product 1

HCID 86710422HCID 86710422, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-8-((2-amino-4-methylpentyl)oxy)-9-iodo-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (130 mg, 0.140 mmol) in 1,4-dioxane (3 mL) was added N-ethyl-N-isopropylpropan-2-amine (54.2 mg, 0.419 mmol) and isobenzofuran-1,3-dione (24.83 mg, 0.168 mmol). The reaction mixture was refluxed for 16 h. After cooling, the reaction mixture was diluted with EtOAc (10 mL). The organics were washed with water, saturated aqueous NaHCO3. The combined aqueous layers were extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative TLC plate using 2% Methanol: DCM as a eluent system to afford (S)-2-(1-((9-iodo-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (85 mg, 0.084 mmol, 60% yield) as a pale yellow solid. LC/MS (ESI) m/e 596.5 [(M+H)+, calcd for C28H27IN3O4 596.1] LC/MS retention time (method E): tR=1.3 min.

Workup

  1. temperatureThe reaction mixture was refluxed for 16 h
  2. temperatureAfter cooling
  3. washThe organics were washed with water, saturated aqueous NaHCO3
  4. extractionThe combined aqueous layers were extracted with ethyl acetate (3×10 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative TLC plate

Sources & evidence

ORD record
ord-4a217e42a47f49d8924cd314562db6d8
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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