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Dibutyltin dichloride → 3-{4-[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}-2-methyl-propionic acid

HRID 1877415
ノート
印刷プレビュー

反応式

HRID 1877415 の反応式
[Cl:1][C:2]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:3]=1[O:4][C:5]1[C:10]([C:11]([N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][CH2:15][CH2:14]2)=[O:12])=[CH:9][C:8]([F:23])=[CH:7][N:6]=1.C[O:30][C:31](=[O:36])[CH:32]([CH3:35])[CH:33]=O.C([Sn](Cl)(Cl)CCCC)CCC.C1([SiH3])C=CC=CC=1>O.C1COCC1>[Cl:1][C:2]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:3]=1[O:4][C:5]1[C:10]([C:11]([N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]([CH2:33][CH:32]([CH3:35])[C:31]([OH:36])=[O:30])[CH2:15][CH2:14]2)=[O:12])=[CH:9][C:8]([F:23])=[CH:7][N:6]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 12688Dibutyltin dichlorideHCID 12752PhenylsilaneHCID 103507Propanoic acid, 2-methyl-3-oxo-, methyl esterHCID 59294514[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone

生成物 1

HCID 592945113-{4-[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}-2-methyl-propionic acid
収率 7.3%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
150 °C

実験手順

To a solution of [2-(2,5-dichloro-phenoxy)-5-fluoro-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (25.1 mg, 0.06 mmol, 1.0 equiv; Example 147) in a 1:1 mixture of THF and water (1 mL) was added 2-methyl-3-oxo-propionic acid methyl ester (27.9 mg, 0.24 mmol, 4.0 equiv; [CAS RN 51673-64-4]), dibutyltin dichloride (1.8 mg, 0.006 mmol, 0.1 equiv; [CAS RN 683-18-1]) and phenylsilane (13.0 mg, 15 μL, 0.12 mmol, 2.0 equiv; [CAS RN 694-53-1]). The reaction mixture was heated by microwave irradiation to 150° C. for 1.5 h. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 2.2 mg (7%) of the title compound as a light yellow solid. MS (ISP): 504.0 [M+H]+.

後処理

  1. customRemoval of the solvent mixture
  2. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  3. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  4. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

出典と根拠

ORDレコード
ord-b69d06ea730340ea88049a9c723c45aa
出典データセット
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08309734B2

反応ノート

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