Sodium Carbonate → 2-[5-(4-Amino-3-nitro-5-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-ol

HRID 1261719ノート

反応式

HRID 1261719 の反応式
Br[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:12][CH2:11][CH2:10][O:9]2)[C:5]([NH:13]C(=O)C(F)(F)F)=[C:4]([N+:20]([O-:22])=[O:21])[CH:3]=1.CC1(C)C(C)(C)OB([C:31]2[CH:32]=[N:33][C:34]([C:37]([OH:40])([CH3:39])[CH3:38])=[N:35][CH:36]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>CCOC(C)=O.O.ClCCl.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[NH2:13][C:5]1[C:6]([CH:8]2[CH2:12][CH2:11][CH2:10][O:9]2)=[CH:7][C:2]([C:31]2[CH:32]=[N:33][C:34]([C:37]([OH:40])([CH3:39])[CH3:38])=[N:35][CH:36]=2)=[CH:3][C:4]=1[N+:20]([O-:22])=[O:21]

参加物

8

反応物 4

HCID 10340Sodium Carbonate2 回HCID 312751,4-DioxaneHCID 665203402-[5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]propan-2-olHCID 71551840N-(4-bromo-2-nitro-6-tetrahydrofuran-2-yl-phenyl)-2,2,2-trifluoro-acetamide

生成物 1

HCID 681081992-[5-(4-Amino-3-nitro-5-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-ol

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

N-(4-Bromo-2-nitro-6-tetrahydrofuran-2-yl-phenyl)-2,2,2-trifluoro-acetamide (6) (19.00 g, 49.59 mmol), 2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]propan-2-ol (7) (14.41 g, 54.55 mmol), aqueous 2.7 M sodium carbonate (73.48 mL, 198.4 mmol), and 1,4-dioxane (190 mL, Sigma-Aldrich 360481) were mixed. A stream of nitrogen was bubbled through the stirring mixture for 40 minutes, followed by addition of 1,1′-bis(diphenylphosphino)ferrocene dichloropalladium dichloromethane adduct (2.025 g, 2.480 mmol, Strem 460450). The reaction mixture was stirred at reflux under N2 for 7 hrs, added another 50 mL of saturated aqueous sodium carbonate, and refluxed for another 16 hrs. The reaction mixture was allowed to cool, then diluted with EtOAc (500 mL) and water (200 mL). The layers were separated and the aqueous phase extracted with EtOAc (200 mL). The combined organic phase was washed with water (500 mL), brine (500 mL), dried over Na2SO4, filtered through a Florisil® plug, and concentrated on a rotary evaporator to give crude (8) as an orange oil. Purified by ISCO silica gel chromatography eluting with 20-90% EtOAc/hexane to give (8) as an orange solid (15.00 g, 81-88% purity). LCMS (C18 column eluting with 10-90% CH3CN/water gradient over 5 minutes with formic acid modifier) M+1: 345.35 (2.68 min). 1H NMR (300 MHz, CDCl3) δ 8.88 (s, 2H), 8.36 (d, J=2.2 Hz, 1H), 7.56 (d, J=2.1 Hz, 1H), 7.09 (s, 2H), 4.92 (t, J=7.2 Hz, 1H), 4.62 (s, 1H), 4.20-4.11 (m, 1H), 4.03-3.94 (m, 1H), 2.39-2.26 (m, 1H), 2.23-2.08 (m, 3H), 1.64 (s, 6H) ppm.

後処理

  1. customA stream of nitrogen was bubbled through the stirring mixture for 40 minutes
  2. temperatureat reflux under N2 for 7 hrs
  3. temperaturerefluxed for another 16 hrs
  4. temperatureto cool
  5. customThe layers were separated
  6. extractionthe aqueous phase extracted with EtOAc (200 mL)
  7. washThe combined organic phase was washed with water (500 mL), brine (500 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered through a Florisil® plug
  10. concentrationconcentrated on a rotary evaporator

出典と根拠

ORDレコード
ord-a0d6551ea05146229e20320e6dad5143
出典データセット
uspto-grants-2013_06
特許番号
US08471014B2

反応ノート

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