Cesium carbonate → N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoro methyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-3-fluorophenyl) acetamide

HRID 1428578ノート

反応式

HRID 1428578 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]([CH2:18][C:19]([CH3:30])([CH3:29])[CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])=[C:14]([C:31]([F:34])([F:33])[F:32])[CH:13]=2)=[O:10])=[CH:4][C:3]=1[F:35].[CH2:36]([O:38][C:39]1[C:40]([O:54][CH2:55][C:56]2[CH:61]=[CH:60][C:59]([O:62][CH3:63])=[CH:58][CH:57]=2)=[N:41][CH:42]=[C:43](B2OC(C)(C)C(C)(C)O2)[CH:44]=1)[CH3:37].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]>[Si:22]([O:21][CH2:20][C:19]([CH3:30])([CH3:29])[CH2:18][C:15]1[CH:16]=[CH:17][C:12]([NH:11][C:9](=[O:10])[CH2:8][C:5]2[CH:6]=[CH:7][C:2]([C:43]3[CH:42]=[N:41][C:40]([O:54][CH2:55][C:56]4[CH:57]=[CH:58][C:59]([O:62][CH3:63])=[CH:60][CH:61]=4)=[C:39]([O:38][CH2:36][CH3:37])[CH:44]=3)=[C:3]([F:35])[CH:4]=2)=[CH:13][C:14]=1[C:31]([F:34])([F:33])[F:32])([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 904156982-(4-bromo-3-fluorophenyl)-N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamideHCID 904167753-Ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

生成物 1

HCID 90415650N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoro methyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-3-fluorophenyl) acetamide収率 80%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

A solution of 2-(4-bromo-3-fluorophenyl)-N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide (80 mg, 0.139 mmol), 3-ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (53.5 mg, 0.139 mmol), Cs2CO3 (90 mg, 0.278 mmol), PdCl2(dppf) (10.15 mg, 0.014 mmol) in 1,4-dioxane (9 mL) and H2O (3 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 EA (60 mL) and washed with H2O (20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by preparative TLC (PE/EA=2/1) to yield N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-3-fluorophenyl)acetamide (100 mg, 0.111 mmol, 80.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.84 (d, J=2.0 Hz, 1H), 7.77 (s, 1H), 7.37 (d, J=7.6 Hz, 1H), 7.34-7.30 (m, 5H), 7.17-7.15 (m, 2H), 6.83 (d, J=8.8 Hz, 2H), 5.27 (s, 2H), 4.04-3.99 (m, 4H), 3.70 (s, 3H), 3.66 (s, 2H), 3.24 (s, 2H), 2.69 (s, 2H), 1.31 (t, J=7.0 Hz, 3H), 0.86 (s, 9H), 0.73 (s, 6H), 0.00 (s, 6H); ES-LCMS m/z 755.2 (M+H).

後処理

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in EA (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 material was purified by preparative TLC (PE/EA=2/1)

出典と根拠

ORDレコード
ord-3593d4a344934f3f81cf67331ea900b9
出典データセット
uspto-grants-2015_01
特許番号
US08937071B2

反応ノート

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