Citric Acid → 3-{2-[6-(Tetrahydro-pyran-2-yloxycarbamoyl)-hexylcarbamoyl]-1H-indol-5-yl}-propionic acid ethyl ester

HRID 548256Notes

Reaction equation

HRID 548256 reaction equation
[CH2:1]([O:3][C:4](/[CH:6]=[CH:7]/[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]([C:17]([OH:19])=O)=[CH:11]2)=[O:5])[CH3:2].CC[N:22]=C=NCCCN(C)C.Cl.Cl.CCN(CC)CC.C1C=CC2N(O)N=NC=2C=1.[O:50]1[CH2:55][CH2:54][CH2:53][CH2:52][CH:51]1[O:56][NH:57][C:58](=[O:66])[CH:59](N)[CH2:60][CH2:61][CH2:62][CH2:63][CH3:64].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.O>[CH2:1]([O:3][C:4](=[O:5])[CH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]([C:17](=[O:19])[NH:22][CH2:64][CH2:63][CH2:62][CH2:61][CH2:60][CH2:59][C:58](=[O:66])[NH:57][O:56][CH:51]1[CH2:52][CH2:53][CH2:54][CH2:55][O:50]1)=[CH:11]2)[CH3:2]

Participants

10

Reactant 7

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 579716455-((E)-2-Ethoxycarbonyl-vinyl)-1H-indole-2-carboxylic acidHCID 86636515Amino heptanoic acid (tetrahydropyran-2-yloxy)amide

Product 1

HCID 579716953-{2-[6-(Tetrahydro-pyran-2-yloxycarbamoyl)-hexylcarbamoyl]-1H-indol-5-yl}-propionic acid ethyl esterYield 69%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-((E)-2-Ethoxycarbonyl-vinyl)-1H-indole-2-carboxylic acid (0.427 g, 1.6 mmol) was dissolved in anhydrous DMF (20 ml). EDCl.HCl (0.38 g, 2 mmol), Et3N (0.59 ml, 4.3 mmol), HOBt (0.27 g, 2 mmol) and 7 amino heptanoic acid (tetrahydropyran-2-yloxy) amide (0.4 g, 1.6 mmol in anhydrous DMF 20 ml) were added and the reaction stirred at room temperature for 16 h under nitrogen. Water was added, the reaction mixture acidified to pH=6-7 (10% citric acid) and extracted with DCM. The organic layer was washed with 10% citric acid and saturated sodium hydrogen carbonate (×2). The solvent was removed in vacuo to give crude product which was purified by chromatography (EtOAc:hexane 1:2→EtOAc) to give the required product as a yellow solid (550 mg, 69% yield). LCMS purity 93%, m/z 488 [M++H]+

Workup

  1. extractionextracted with DCM
  2. washThe organic layer was washed with 10% citric acid and saturated sodium hydrogen carbonate (×2)
  3. customThe solvent was removed in vacuo
  4. customto give crude product which
  5. customwas purified by chromatography (EtOAc:hexane 1:2→EtOAc)

Sources & evidence

ORD record
ord-14600f05fc594e4f892c16c07f9056d4
Source dataset
uspto-grants-2011_05
Patent number
US07939666B2

Reaction notes

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