Diisopropylethylamine → 2-(((2S,3R)-1-(5-Fluoro-2-iodobenzoyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

HRID 61175Notes

Reaction equation

HRID 61175 reaction equation
[CH3:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][NH:4][C@@H:3]1[CH2:8][N:9]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]1=[O:19].[F:20][C:21]1[CH:22]=[CH:23][C:24]([I:30])=[C:25]([CH:29]=1)[C:26](O)=[O:27].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC(N(C)C)=O.CCOC(C)=O>[F:20][C:21]1[CH:22]=[CH:23][C:24]([I:30])=[C:25]([CH:29]=1)[C:26]([N:4]1[CH2:5][CH2:6][CH2:7][C@@H:2]([CH3:1])[C@H:3]1[CH2:8][N:9]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]1=[O:19])=[O:27]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131585835-Fluoro-2-iodobenzoic acidHCID 1177276302-(((2S,3R)-3-Methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

Product 1

HCID 1177280012-(((2S,3R)-1-(5-Fluoro-2-iodobenzoyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dioneYield 62.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a stirred solution of 2-(((2S,3R)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione (440 mg, 1.70 mmol), 5-fluoro-2-iodobenzoic acid (543 mg, 2.04 mmol), and DIPEA (438 mg, 3.40 mmol) in anhydrous DMA (10 mL) was added HATU (971 mg, 2.55 mmol) at rt under nitrogen and the reaction stirred for 16 h. The reaction mixture was diluted with EtOAc (100 mL), washed with 10% aq. LiCl (3×50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (0% to 70% EtOAc/hexanes) to afford the title compound as a yellow oil (537 mg, 62%). ESI MS (M+H) 507.

Workup

  1. washwashed with 10% aq. LiCl (3×50 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography on silica gel (0% to 70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5184f6eb692d4b8db2afcc227ffd7a70
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

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