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

HRID 1430985노트

반응식

HRID 1430985 반응식
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]

참가 물질

7

반응물 3

HCID 8471TriethylamineHCID 58528906N-(5-bromo-pyridin-2-yl)-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamideHCID 178476777HCID 178476777, 화합물

생성물 1

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

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 1140Toluene용매HCID 6344Dichloromethane용매

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온도
90 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-09a5c6d1837e47baa2e615ca8cb126b6
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940927B2

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