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Cesium carbonate → N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,3-difluorophenyl)acetamide

HRID 1428568
ノート
印刷プレビュー

反応式

HRID 1428568 の反応式
[CH2:1]([O:3][C:4]1[C:5]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)=[N:6][CH:7]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:9]=1)[CH3:2].[CH2:29]([O:36][CH2:37][CH2:38][O:39][C:40]1[CH:45]=[CH:44][C:43]([NH:46][C:47](=[O:58])[CH2:48][C:49]2[CH:54]=[CH:53][C:52](Br)=[C:51]([F:56])[C:50]=2[F:57])=[CH:42][C:41]=1[C:59]([F:62])([F:61])[F:60])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.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]>[CH2:29]([O:36][CH2:37][CH2:38][O:39][C:40]1[CH:45]=[CH:44][C:43]([NH:46][C:47](=[O:58])[CH2:48][C:49]2[CH:54]=[CH:53][C:52]([C:8]3[CH:7]=[N:6][C:5]([O:19][CH2:20][C:21]4[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=4)=[C:4]([O:3][CH2:1][CH3:2])[CH:9]=3)=[C:51]([F:56])[C:50]=2[F:57])=[CH:42][C:41]=1[C:59]([F:61])([F:60])[F:62])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=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 3

HCID 10796Cesium carbonateHCID 904167753-Ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 90417511N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-bromo-2,3-difluorophenyl)acetamide

生成物 1

HCID 90416445N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,3-difluorophenyl)acetamide収率 54.5%

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

To a solution of 3-ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (8.49 mg, 0.022 mmol), N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-bromo-2,3-difluorophenyl)acetamide (12 mg, 0.022 mmol) and Cs2CO3 (17.96 mg, 0.055 mmol) in 1,4-dioxane (6 mL) and H2O (2 mL) stirred under a N2 atmosphere at 20° C. was added PdCl2(dppf) (0.807 mg, 1.102 μmol) in one charge. The reaction vessel was heated in 110° C. for 3 h. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by preparative TLC (PE/EA=2:1, Rf=0.6) to yield a brown solid of N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,3-difluorophenyl)acetamide (10 mg, 0.012 mmol, 52.7% yield): 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J=3.0 Hz, 1H), 7.66-7.50 (m, 2H), 7.41-7.34 (m, 2H), 7.29-7.07 (m, 8H), 6.95-6.80 (m, 3H), 5.39 (d, J=4.9 Hz, 2H), 4.57 (d, J=5.0 Hz, 2H), 4.14 (d, J=4.0 Hz, 2H), 4.09-3.96 (m, 2H), 3.84-3.66 (m, 7H), 1.38 (q, J=6.4 Hz, 3H); ES-LCMS m/z 723.1 (M+H).

後処理

  1. additioncharge
  2. concentrationThen the solution was concentrated
  3. extractionThe combined organic extract
  4. washwas washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by preparative TLC (PE/EA=2:1, Rf=0.6)

出典と根拠

ORDレコード
ord-2fa6edf0a4f74f7f894fa36f698672eb
出典データセット
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08937071B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート