Dichloromethane → {4-[(Pyrid-3-yl)ethynyl]-2-phenylbenzoyl]methionine methyl ester

HRID 2121191노트

반응식

HRID 2121191 반응식
[CH3:1][O:2][C:3](=[O:25])[C@H:4]([CH2:21][CH2:22][S:23][CH3:24])[NH:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10](I)=[CH:9][C:8]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.ClCCl.[C:29]([Sn](CCCC)(CCCC)CCCC)#[CH:30].[I-].Br[C:46]1[CH:47]=[N:48][CH:49]=[CH:50][CH:51]=1.C(N(CC)CC)C>CN(C=O)C.CCOCC.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3](=[O:25])[C@H:4]([CH2:21][CH2:22][S:23][CH3:24])[NH:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([C:29]#[C:30][C:46]2[CH:47]=[N:48][CH:49]=[CH:50][CH:51]=2)=[CH:9][C:8]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

참가 물질

11

반응물 6

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 122863-BromopyridineHCID 30165Iodide IonHCID 621176EthynyltributyltinHCID 53801632(4-Iodo-2-phenylbenzoyl)methionine methyl ester

생성물 1

HCID 20622839{4-[(Pyrid-3-yl)ethynyl]-2-phenylbenzoyl]methionine methyl ester수율 24%

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

A mixture of (4-iodo-2-phenylbenzoyl)methionine methyl ester, prepared as in Example 210D, (469 mg, 1.0 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride, complexed to dichloromethane (1:1) (82 mg, 0.10 mmol), and ethynyltributyltin (315 mg, 1.0 mmol) in DMF (5 mL) was heated at 80° C. for 6 hours at which point thin layer chromatography indicated no starting iodide left. 3-Bromopyridine (0.114 mL, 1.2 mmol) and triethylamine (0.42 mL, 3.0 mmol) were added and the reaction mixture was heated at 100° C. for 14 hours. The reaction mixture was diluted with ether (50 mL) and ethyl acetate (50 mL), washed with water and brine, dried over anhydrous magnesium sulfate, and filtered. To the filtrate was added 3 drops of water, followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (0.2 mL) with swirling. The resulting milky mixture was filtered through silica gel (15 g), rinsed with ethyl acetate, and concentrated in vacuo. The residue was then purified by column chromatography (50% ethyl acetate-hexane, then ethyl acetate) to give {4-[(pyrid-3-yl)ethynyl]-2-phenylbenzoyl}methionine methyl ester (109 mg, 24%). 1H NMR (300 MHz, CDCl3) δ 8.79 (s, 1H), 8.58 (dd, 1H), 7.82 (dt, 1H), 7.74 (d, 1H), 7.59 (dd, 1H), 7.57 (s, 1H), 7.45 (m, 5H), 7.31 (dd, 1H), 5.93 (br d, 1H), 4.69 (m, 1H), 3.68 (s, 3H), 2.08 (m, 2H), 2.02 (s, 3H), 1.93 (m, 1H), 1.76 (m, 1H). MS (CI+) m/e 445 (M+H)+.

후처리

  1. waitleft
  2. temperaturethe reaction mixture was heated at 100° C. for 14 hours
  3. washwashed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. additionTo the filtrate was added 3 drops of water
  7. filtrationThe resulting milky mixture was filtered through silica gel (15 g)
  8. washrinsed with ethyl acetate
  9. concentrationconcentrated in vacuo
  10. customThe residue was then purified by column chromatography (50% ethyl acetate-hexane

출처 및 근거

ORD 기록
ord-f581f5f8742d4882aecd016f46288241
출처 데이터셋
uspto-grants-2004_02
특허 번호
US06693123B2

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