Dimethylbarbituric acid → Ethyl tert-butoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate

HRID 63963

반응식

HRID 63963 반응식
C([O:4][C:5]1[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:6]=1[C:12]1[C:17]([CH:18]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:16]([CH3:29])[N:15]=[C:14]2[S:30][C:31]3[CH2:36][CH2:35][CH2:34][CH2:33][C:32]=3[C:13]=12)C=C.CN1C(=O)CC(=O)N(C)C1=O>ClCCl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[C:25]([O:24][CH:18]([C:17]1[C:12]([C:6]2[CH:7]=[CH:8][C:9]([CH3:11])=[CH:10][C:5]=2[OH:4])=[C:13]2[C:32]3[CH2:33][CH2:34][CH2:35][CH2:36][C:31]=3[S:30][C:14]2=[N:15][C:16]=1[CH3:29])[C:19]([O:21][CH2:22][CH3:23])=[O:20])([CH3:28])([CH3:26])[CH3:27]

참가 물질

5

반응물 2

HCID 69860Dimethylbarbituric acidHCID 67890974Ethyl {4-[2-(allyloxy)-4-methylphenyl]-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl}(tert-butoxy)acetate

생성물 1

HCID 136372356Ethyl tert-butoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate수율 63%

시약·촉매·용매 2

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매2회HCID 6344Dichloromethane용매

실험 절차

To a stirred solution of ethyl {4-[2-(allyloxy)-4-methylphenyl]-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl}(tert-butoxy)acetate (Step 8, 370 mg, 729 μmol) in dichloromethane (10 mL) was added 1,3-dimethylbarbituric acid (569 mg, 3.64 mmol), and the reaction was evacuated and filed with nitrogen. Palladium tetrakis(triphenylphosphine) (17 mg, 15 μmol) was added and the reaction was heated to reflux for 16 hours. Further palladium tetrakis(triphenylphosphine) (17 mg, 15 μmol) was added and the reaction was heated to reflux for a further 4 hours. The reaction was concentrated in vacuo and preabsorbed onto silica. The residue was purified using ISCO Companion with a Redisep silica gel 12 g cartridge and a gradient of heptane and ethyl acetate (0% to 20%). Product containing fractions were concentrated in vacuo to give the title compound as a pair of diastereoisomers as a colourless oil, 214 mg, in a 63% yield. The other pair of minor diastereoisomers co-eluted with unreacted starting material and were not isolated. LC-MS (12 min acidic) 6.89 mins 100% pure by UV, ES+/APCI+ 468, ES−/APCI− 466 1H NMR (400 MHz, CDCl3) δ ppm 1.01 (s, 9 H) 1.20 (t, 3 H) 1.62-1.85 (m, 4 H) 2.02-2.14 (m, 2 H) 2.41 (s, 3 H) 2.74 (s, 3 H) 2.78-2.85 (m, 2 H) 4.08-4.18 (m, 2 H) 5.14 (s, 1 H) 6.78 (s, 1 H) 6.82 (d, 1 H) 7.17 (d, 1 H).

후처리

  1. customthe reaction was evacuated
  2. temperaturethe reaction was heated
  3. temperatureto reflux for 16 hours
  4. temperaturethe reaction was heated
  5. temperatureto reflux for a further 4 hours
  6. concentrationThe reaction was concentrated in vacuo
  7. custompreabsorbed onto silica
  8. customThe residue was purified
  9. additionProduct containing fractions
  10. concentrationwere concentrated in vacuo

출처 및 근거

ORD 기록
ord-3428941d54bc4857922d6189769ab759
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447116B2

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