Dimethylbarbituric acid → Ethoxy-[4-(2-hydroxy-4-methyl-phenyl)-2-methyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-b]pyridin-3-yl]-acetic acid ethyl ester

HRID 2406385Notes

Reaction equation

HRID 2406385 reaction equation
[CH2:1]([O:3][C:4](=[O:34])[CH:5]([C:9]1[C:10]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=2[O:30]CC=C)=[C:11]2[C:18]3[CH2:19][CH2:20][CH2:21][CH2:22][C:17]=3[S:16][C:12]2=[N:13][C:14]=1[CH3:15])[O:6][CH2:7][CH3:8])[CH3:2].CN1C(=O)CC(=O)N(C)C1=O>ClCCl>[CH2:1]([O:3][C:4](=[O:34])[CH:5]([O:6][CH2:7][CH3:8])[C:9]1[C:10]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=2[OH:30])=[C:11]2[C:18]3[CH2:19][CH2:20][CH2:21][CH2:22][C:17]=3[S:16][C:12]2=[N:13][C:14]=1[CH3:15])[CH3:2]

Participants

4

Reactant 2

HCID 69860Dimethylbarbituric acidHCID 69672825[4-(2-Allyloxy-4-methyl-phenyl)-2-methyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-b]pyridin-3-yl]-ethoxy-acetic acid ethyl ester

Product 1

HCID 136372354Ethoxy-[4-(2-hydroxy-4-methyl-phenyl)-2-methyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-b]pyridin-3-yl]-acetic acid ethyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of [4-(2-Allyloxy-4-methyl-phenyl)-2-methyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-b]pyridin-3-yl]-ethoxy-acetic acid ethyl ester (22 mg, 46 μmols) in dichloromethane (3 mL) was added 1,3-dimethylbarbituric acid (38 mg, 240 μmols, 5 eq), and the reaction was evacuated and filled with nitrogen. Palladium tetrakis(triphenylphosphine) (1.2 mg, 2 mol %) was added and the reaction was heated to reflux for 16 hours. The reaction was concentrated in vacuo. The residue was purified using ISCO Companion with a Redisep silica gel 4 g cartridge and a gradient of heptane and ethyl acetate (0% to 40%). Fractions containing desired product were combined and concentrated in vacuo to give ethoxy-[4-(2-hydroxy-4-methyl-phenyl)-2-methyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-b]pyridin-3-yl]-acetic acid ethyl ester as a pale yellow oil, 20 mg (95% yield). LC-MS (12 min acidic) 6.40 mins 58-69% pure by UV, ES+/APCI+ 440, ES−/APCI− 438; 6.66 mins 27-31% pure by UV, ES+/APCI+ 440, ES−/APCI− 438.

Workup

  1. customthe reaction was evacuated
  2. additionfilled with nitrogen
  3. additionPalladium tetrakis(triphenylphosphine) (1.2 mg, 2 mol %) was added
  4. temperaturethe reaction was heated
  5. temperatureto reflux for 16 hours
  6. concentrationThe reaction was concentrated in vacuo
  7. customThe residue was purified
  8. additionFractions containing desired product
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4fe44091cf1e44898f419f82a233cfbf
Source dataset
uspto-grants-2014_08
Patent number
US08809363B2

Reaction notes

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