(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 1294604Notes

Reaction equation

HRID 1294604 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-fbfcfc648c1c4ae58586d51550321c9d
Source dataset
uspto-grants-2007_07
Patent number
US07241772B2

Reaction notes

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