(2-{[3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyrylamino]-methyl}-pyridin-3-yloxy)-acetic acid ethyl ester → {3-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2-methyl-propyl]-imidazo[1,5-a]pyridin-8-yloxy}-acetic acid ethyl ester

HRID 852229Notes

Reaction equation

HRID 852229 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[CH2:5][O:6][C:7]1[C:8]([CH2:13][NH:14][C:15](=O)[CH2:16][C:17]([N:20]2[C:28](=[O:29])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]2=[O:30])([CH3:19])[CH3:18])=[N:9][CH:10]=[CH:11][CH:12]=1)[CH3:2]>P(Cl)(Cl)(Cl)=O>[CH2:1]([O:3][C:4](=[O:32])[CH2:5][O:6][C:7]1[C:8]2[N:9]([C:15]([CH2:16][C:17]([N:20]3[C:28](=[O:29])[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[C:21]3=[O:30])([CH3:19])[CH3:18])=[N:14][CH:13]=2)[CH:10]=[CH:11][CH:12]=1)[CH3:2]

Participants

3

Reactant 1

HCID 69158493(2-{[3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyrylamino]-methyl}-pyridin-3-yloxy)-acetic acid ethyl ester

Product 1

HCID 69157841{3-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2-methyl-propyl]-imidazo[1,5-a]pyridin-8-yloxy}-acetic acid ethyl esterYield 55.3%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

A solution of (2-{[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyrylamino]-methyl}-pyridin-3-yloxy)-acetic acid ethyl ester (2.79 g, 6.349 mmol) in 100 ml of neat phosphoryl chloride is stirred at 75° C. for 16 hours. The reaction mixture is poured on 200 g of crushed ice and extracted with methylene chloride. The organic phase is dried over sodium sulfate and evaporated. The residue is purified via flash chromatography on silica gel using a methylene chloride/methylene chloride-ethanolic ammonia gradient (100 to 96:4) to give 1.48 g of {3-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-methyl-propyl]-imidazo[1,5-a]pyridin-8-yloxy}-acetic acid ethyl ester (55%).

Workup

  1. extractionextracted with methylene chloride
  2. dry with materialThe organic phase is dried over sodium sulfate
  3. customevaporated
  4. customThe residue is purified via flash chromatography on silica gel using a methylene chloride/methylene chloride-ethanolic ammonia gradient (100 to 96:4)

Sources & evidence

ORD record
ord-f9ba79097cce49c8980951589ed751da
Source dataset
uspto-grants-2007_08
Patent number
US07253181B2

Reaction notes

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