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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)-2,6-difluorophenyl)acetamide

HRID 576199
ノート
印刷プレビュー

反応式

HRID 576199 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][CH:12]=[N:13][CH:14]=2)O1.[CH2:16]([O:23][CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34](=[O:45])[CH2:35][C:36]2[C:41]([F:42])=[CH:40][C:39](Br)=[CH:38][C:37]=2[F:44])=[CH:29][C:28]=1[C:46]([F:49])([F:48])[F:47])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[C:50]([O-:53])([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].C(Cl)Cl>[CH2:16]([O:23][CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34](=[O:45])[CH2:35][C:36]2[C:41]([F:42])=[CH:40][C:39]([C:11]3[CH:12]=[N:13][C:14]([O:23][CH2:16][C:17]4[CH:22]=[CH:21][C:20]([O:53][CH3:50])=[CH:19][CH:18]=4)=[C:9]([O:26][CH2:25][CH3:24])[CH:10]=3)=[CH:38][C:37]=2[F:44])=[CH:29][C:28]=1[C:46]([F:49])([F:48])[F:47])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
参加物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 27346563-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 90416261N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-bromo-2,6-difluorophenyl)acetamide

生成物 1

HCID 90416829N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,6-difluorophenyl)acetamide収率 70.3%

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒
HCID 962Water溶媒
HCID 312751,4-Dioxane溶媒

実験手順

A solution of 3-ethoxy-2-(4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine (78 mg, 0.202 mmol), N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-bromo-2,6-difluorophenyl)acetamide (110 mg, 0.202 mmol), PdCl2(dppf)-DCM adduct (16.50 mg, 0.020 mmol) and Cs2CO3 (132 mg, 0.404 mmol) in 1,4-dioxane (6 mL) and H2O (2 mL) was stirred at 110° C. for 15 min. After LCMS analysis showed the starting material had disappeared, the solvent was removed in vacuo. The residue was dissolved in DCM (60 mL) and washed with H2O (20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative TLC (DCM/MeOH=10/1) to yield N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,6-difluorophenyl)acetamide (70 mg, 0.071 mmol, 35.1% yield): 1H NMR (400 MHz, CD3OD) δ 7.97 (d, J=2.0 Hz, 1H), 7.84 (s, 1H), 7.71 (d, J=11.2 Hz, 1H), 7.46 (d, J=2.0 Hz, 1H), 7.39 (d, J=8.6 Hz, 2H), 7.37-7.13 (m, 8H), 6.90 (d, J=8.6 Hz, 2H), 5.39-5.34 (m, 2H), 4.61 (s, 2H), 4.27-4.20 (m, 2H), 4.18-4.10 (m, 2H), 3.86-3.82 (m, 2H), 3.78 (s, 3H), 1.42 (t, J=6.9 Hz, 3H), 1.19 (s, 2H); ES-LCMS m/z 723.2 (M+H).

後処理

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in DCM (60 mL)
  3. washwashed with H2O (20 mL) and brine (20 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by preparative TLC (DCM/MeOH=10/1)

出典と根拠

ORDレコード
ord-9681ffb449be4aa58dbc97f245d31d81
出典データセット
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09035063B2

反応ノート

読み込み中…

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