Cesium carbonate → 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-2-fluorophenyl)-N-(6-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)pyridin-3-yl)acetamide

HRID 576209ノート

反応式

HRID 576209 の反応式
[CH3:1][N:2]([CH3:36])[CH2:3][CH2:4][O:5][C:6]1[N:11]=[CH:10][C:9]([NH:12][C:13](=[O:31])[CH2:14][C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[CH:17][C:16]=2[F:30])=[CH:8][C:7]=1[C:32]([F:35])([F:34])[F:33].[CH2:37]([O:44][C:45]1[CH:50]=[C:49]([O:51][CH2:52][CH3:53])[C:48](I)=[CH:47][N:46]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=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]>[CH2:37]([O:44][C:45]1[N:46]=[CH:47][C:48]([C:18]2[CH:19]=[CH:20][C:15]([CH2:14][C:13]([NH:12][C:9]3[CH:10]=[N:11][C:6]([O:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:36])=[C:7]([C:32]([F:33])([F:34])[F:35])[CH:8]=3)=[O:31])=[C:16]([F:30])[CH:17]=2)=[C:49]([O:51][CH2:52][CH3:53])[CH:50]=1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 90415933N-(6-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)pyridin-3-yl)-2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamideHCID 904176602-(Benzyloxy)-4-ethoxy-5-iodopyridine

生成物 1

HCID 904155782-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-2-fluorophenyl)-N-(6-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)pyridin-3-yl)acetamide収率 11.9%

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 N-(6-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)pyridin-3-yl)-2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide (30 mg, 0.059 mmol), 2-(benzyloxy)-4-ethoxy-5-iodopyridine (20.84 mg, 0.059 mmol), PdCl2(dppf) (42.9 mg, 0.059 mmol) and Cs2CO3 (19.12 mg, 0.059 mmol) in 1,4-dioxane (3 mL) and H2O (1 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 (30 mL) and washed with H2O (10 mL) and brine (10 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 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-2-fluorophenyl)-N-(6-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)pyridin-3-yl)acetamide (5 mg, 6.97 μmol, 11.9% yield): 1H NMR (400 MHz, CD3OD) δ 8.56 (s, 1H), 8.33 (d, J=2.0 Hz, 1H), 7.99 (s, 1H), 7.48-7.30 (m, 8H), 6.51 (s, 1H), 5.38 (s, 2H), 4.64 (t, J=5.2 Hz, 2H), 4.16 (m, 2H), 3.84 (s, 2H), 3.03 (t, J=5.2 Hz, 2H), 2.53 (s, 6H), 1.40 (t, J=7.0 Hz, 3H); ES-LCMS m/z 613.1 (M+H).

後処理

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in EA (30 mL)
  3. washwashed with H2O (10 mL) and brine (10 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-dff1b87a9b834cb48df07500a078e3b7
出典データセット
uspto-grants-2015_05
特許番号
US09035063B2

反応ノート

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