Triethylamine → {6-[3-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoylamino]-pyridin-3-yl}-methyl-phosphinic acid ethyl ester

HRID 1430985ノート

反応式

HRID 1430985 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:28])[C:10]2[CH:15]=[C:14]([O:16][CH2:17][CH2:18][C:19]3[CH:23]=[CH:22][S:21][CH:20]=3)[CH:13]=[C:12]([O:24][CH:25]([CH3:27])[CH3:26])[CH:11]=2)=[N:6][CH:7]=1.[CH2:29]([O:31][PH:32]([CH3:34])=[O:33])[CH3:30].CCN(CC)CC>C1(C)C=CC=CC=1.C(Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH2:29]([O:31][P:32]([C:2]1[CH:7]=[N:6][C:5]([NH:8][C:9](=[O:28])[C:10]2[CH:15]=[C:14]([O:16][CH2:17][CH2:18][C:19]3[CH:23]=[CH:22][S:21][CH:20]=3)[CH:13]=[C:12]([O:24][CH:25]([CH3:27])[CH3:26])[CH:11]=2)=[CH:4][CH:3]=1)([CH3:34])=[O:33])[CH3:30]

参加物

7

反応物 3

HCID 8471TriethylamineHCID 58528906N-(5-bromo-pyridin-2-yl)-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamideHCID 178476777HCID 178476777、化合物

生成物 1

HCID 58528997{6-[3-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoylamino]-pyridin-3-yl}-methyl-phosphinic acid ethyl ester収率 92.3%

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
90 °C

実験手順

To a stirred solution of N-(5-bromo-pyridin-2-yl)-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamide (1.69 g, 3.66 mmol) in toluene (40 mL) was added a solution of methylphosphinic acid ethyl ester (0.475 g, 4.40 mmol), palladium tetrakis(triphenylphosphine) (0.846 g, 0.733 mmol), and Et3N (1.54 mL, 10.9 mmol) in DCM (5.0 mL) at rt. The mixture was heated at 90° C. overnight. Cooled to rt and concentrated. EtOAc and water were added and the mixture was filtered through a pad of Celite to remove the insoluble solids. The organic layer was separated, washed with brine (1×), dried with anhydrous MgSO4, filtered, and concentrated. The residue was purified by silica gel flash chromatography (6×25 cm, hexane/EtOAc, v/v=1:3, EtOAc, 1% MeOH in EtOAc). Fractions containing the product were pooled and concentrated to give {6-[3-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoylamino]-pyridin-3-yl}-methyl-phosphinic acid ethyl ester (1.65 g, 92%) as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 8.74 (br, 1H), 8.68 (ddd, J=6, 2, 1 Hz, 1H), 8.49 (ddd, J=9, 2, 1 Hz, 1H). 8.10 (ddd, J=11, 9, 2 Hz, 1H), 7.63-7.70 (m, 1H), 7.43-7.47 (m, 1H), 7.29 (dd, J=5.3 Hz, 1H), 7.09-7.10 (m, 1H), 7.04 (dd, J=5, 1 Hz, 1H), 6.99-7.03 (m, 2H), 6.64 (m, 1H), 4.60 (m, 1H), 4.22 (t, J=7 Hz, 2H), 4.07-4.15 (m, 1H), 3.84-3.92 (m, 1H), 3.14 (t, J=7 Hz, 2H), 1.70 (d, J=15 Hz, 3H), 1.35 (d, J=6 Hz, 6H), 1.23-1.31 (m, 3H).

後処理

  1. temperatureCooled to rt
  2. concentrationconcentrated
  3. additionEtOAc and water were added
  4. filtrationthe mixture was filtered through a pad of Celite
  5. customto remove the insoluble solids
  6. customThe organic layer was separated
  7. washwashed with brine (1×)
  8. dry with materialdried with anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel flash chromatography (6×25 cm, hexane/EtOAc, v/v=1:3, EtOAc, 1% MeOH in EtOAc)
  12. additionFractions containing the product
  13. concentrationconcentrated

出典と根拠

ORDレコード
ord-09a5c6d1837e47baa2e615ca8cb126b6
出典データセット
uspto-grants-2015_01
特許番号
US08940927B2

反応ノート

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