HCID 86710378, compound → HCID 86710377, compound

HRID 1398390Notes

Reaction equation

HRID 1398390 reaction equation
[C:1]([C:4]1[C:20]([O:21][CH2:22][C@@H:23]([N:28]2[C:36](=[O:37])[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:29]2=[O:38])[CH2:24][CH:25]([CH3:27])[CH3:26])=[CH:19][C:7]2[N:8]([CH3:18])[C:9](=[O:17])[C:10]3[C:15]([C:6]=2[CH:5]=1)=[CH:14][CH:13]=[N:12][C:11]=3[CH3:16])(=[O:3])[CH3:2].[CH3:39][Mg]Br>C1COCC1>[OH:3][C:1]([C:4]1[C:20]([O:21][CH2:22][C@@H:23]([N:28]2[C:29](=[O:38])[C:30]3[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:36]2=[O:37])[CH2:24][CH:25]([CH3:27])[CH3:26])=[CH:19][C:7]2[N:8]([CH3:18])[C:9](=[O:17])[C:10]3[C:15]([C:6]=2[CH:5]=1)=[CH:14][CH:13]=[N:12][C:11]=3[CH3:16])([CH3:39])[CH3:2]

Participants

4

Reactant 2

HCID 86710378HCID 86710378, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 86710377HCID 86710377, compoundYield 35.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-2-(1-((9-acetyl-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (220 mg, 0.430 mmol) in THF (6 mL) was added methyl magnesium bromide (1.4 M in diethyl ether) (0.922 mL, 1.290 mmol) at −10° C. and stirred for overnight at RT. The reaction mixture was carefully quenched with water and diluted with EtOAc. The organic layer was separated, dried over sodium sulphate and concentrated under reduced pressure. The residue was purified via silica gel chromatography to afford (S)-2-(1-((9-(2-hydroxypropan-2-yl)-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (0.2 g, 0.152 mmol, 35% yield) as a brown gummy solid. LC/MS (ESI) m/e 528.2 [(M+H)+, calcd for C31H34N3O5 528.2; LC/MS retention time (method D): tR=0.89 min.

Workup

  1. customThe reaction mixture was carefully quenched with water
  2. additiondiluted with EtOAc
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified via silica gel chromatography

Sources & evidence

ORD record
ord-c412ee0e8f044ed78e3d82f684cee624
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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