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Cesium carbonate → N-(3,4-dichlorophenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide

HRID 576228
ノート
印刷プレビュー

反応式

HRID 576228 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)=[O:10])=[C:4]([F:20])[CH:3]=1.[CH2:21]([O:23][C:24]1[C:25]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=2)=[N:26][CH:27]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:29]=1)[CH3:22].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C(Cl)Cl.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]>[Cl:19][C:14]1[CH:13]=[C:12]([NH:11][C:9](=[O:10])[CH2:8][C:5]2[CH:6]=[CH:7][C:2]([C:28]3[CH:27]=[N:26][C:25]([O:39][CH2:40][C:41]4[CH:42]=[CH:43][C:44]([O:47][CH3:48])=[CH:45][CH:46]=4)=[C:24]([O:23][CH2:21][CH3:22])[CH:29]=3)=[CH:3][C:4]=2[F:20])[CH:17]=[CH:16][C:15]=1[Cl:18]
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

8

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 904170062-(4-bromo-2-fluorophenyl)-N-(3,4-dichlorophenyl)acetamide

生成物 1

HCID 90415929N-(3,4-dichlorophenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide収率 52.8%

試薬・触媒・溶媒 4

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
触媒
HCID 962Water溶媒
HCID 6344Dichloromethane溶媒
HCID 312751,4-Dioxane溶媒

反応条件

温度
130 °C

実験手順

To a solution of 2-(4-bromo-2-fluorophenyl)-N-(3,4-dichlorophenyl)acetamide (60 mg, 0.159 mmol), 3-ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (61.3 mg, 0.159 mmol) and Cs2CO3 (156 mg, 0.477 mmol) in 1,4-dioxane (3 mL) and H2O (1 mL) was added PdCl2(dppf) (11.64 mg, 0.016 mmol) in one charge. The mixture was stirred at 130° C. in the microwave for 30 min. After LCMS analysis showed the starting material had disappeared, the mixture was filtered. The filtrate was concentrated and evaporated to dryness to give crude product which was dissolved in DCM and washed with H2O and brine. Then the crude product was purified by preparative TLC (DCM/MeOH=40/1) to give pure product N-(3,4-dichlorophenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (60.0 mg, 0.084 mmol, 52.7% yield): 1H NMR: (400 MHz, CD3OD) δ 7.95 (d, J=2.0 Hz, 1H), 7.92 (d, J=1.8 Hz, 1H), 7.45 (s, 3H), 7.43-7.37 (m, 5H), 6.91 (d, J=8.6 Hz, 2H), 5.37 (s, 2H), 4.15 (m, 3H), 3.79 (s, 4H), 1.42 (t, J=7.0 Hz, 3H); ES-LCMS: m/z 435 (M-120).

後処理

  1. additioncharge
  2. filtrationthe mixture was filtered
  3. concentrationThe filtrate was concentrated
  4. customevaporated to dryness
  5. customto give crude product which
  6. washwashed with H2O and brine
  7. customThen the crude product was purified by preparative TLC (DCM/MeOH=40/1)

出典と根拠

ORDレコード
ord-d6d60a4278e84b7aa16075fb901f8030
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

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