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

HRID 2121191ノート

反応式

HRID 2121191 の反応式
[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

参加物

11

反応物 6

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-f581f5f8742d4882aecd016f46288241
出典データセット
uspto-grants-2004_02
特許番号
US06693123B2

反応ノート

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