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

HRID 852228Notes

Reaction equation

HRID 852228 reaction equation
Cl.Cl.[NH2:3][CH2:4][C:5]1[C:10]([O:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:9][CH:8]=[CH:7][N:6]=1.C(N(CC)CC)C.[CH3:25][C:26]([CH3:42])([N:31]1[C:39](=[O:40])[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32]1=[O:41])[CH2:27][C:28](O)=[O:29]>C(Cl)Cl>[CH2:16]([O:15][C:13](=[O:14])[CH2:12][O:11][C:10]1[C:5]([CH2:4][NH:3][C:28](=[O:29])[CH2:27][C:26]([N:31]2[C:39](=[O:40])[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]2=[O:41])([CH3:42])[CH3:25])=[N:6][CH:7]=[CH:8][CH:9]=1)[CH3:17]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 22038564beta,beta-Dimethyl-1,3dioxo-2-isoindolinepropionic acidHCID 220385702-Aminomethyl-3-(ethoxycarbonylmethoxy)pyridine dihydrochloride

Product 1

HCID 69158493(2-{[3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyrylamino]-methyl}-pyridin-3-yloxy)-acetic acid ethyl esterYield 62.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-aminomethyl-3-(ethoxycarbonylmethoxy)pyridine dihydrochloride (610 mg, 2.155 mmol), triethylamine (732 μl, 5.258 mmol), N,N-dicyclohexylcarbodiimide (596 mg, 2.892 mmol) and 4-(N,N-diemethylamino)-pyridine (10 mg) in 6 ml of dry methylene chloride is added β,β-dimethyl-1,3-dioxo-2-isoindolinepropionic acid (650 mg, 2.629 mmol) at ambient temperature. The mixture is stirred for 24 hours. The precipitate of dicyclohexyl urea is filtered off. The filtrate is evaporated and the residue is purified via flash chromatography on silica gel using a methylene chloride/methylene chloride-ethanolic ammonia gradient (100 to 97:3) to give 591 mg of (2-{[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyrylamino]-methyl}-pyridin-3-yloxy)-acetic acid ethyl ester (46%).

Workup

  1. filtrationThe precipitate of dicyclohexyl urea is filtered off
  2. customThe filtrate is evaporated
  3. customthe residue is purified via flash chromatography on silica gel using a methylene chloride/methylene chloride-ethanolic ammonia gradient (100 to 97:3)

Sources & evidence

ORD record
ord-2ed77c6dd7a34137ad71c7a2c6876512
Source dataset
uspto-grants-2007_08
Patent number
US07253181B2

Reaction notes

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