Diisopropylethylamine → 2-(1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperidin-4-yloxy)-N,N-dimethylacetamide

HRID 1091764노트

반응식

HRID 1091764 반응식
[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:23][N:24]([CH3:35])[C:25](=[O:34])[CH2:26][O:27][CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([N:31]1[CH2:30][CH2:29][CH:28]([O:27][CH2:26][C:25]([N:24]([CH3:35])[CH3:23])=[O:34])[CH2:33][CH2:32]1)=[O:6]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 248117402-Fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acidHCID 43346284N,N-Dimethyl-2-(piperidin-4-yloxy)acetamide

생성물 1

HCID 577918152-(1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperidin-4-yloxy)-N,N-dimethylacetamide수율 61.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (0.2 g, 0.67 mmol), N,N-dimethyl-2-(piperidin-4-yloxy)acetamide (82) (0.125 g, 0.67 mmol) and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (0.215 g, 0.67 mmol) were dissolved in DMF (10 mL), to this was added DIPEA (0.117 mL, 0.67 mmol) and the reaction was stirred for 1 hour. The solvent was evaporated to dryness and the gum was dissolved in acetonitrile (4 mL). The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired material as a cream solid (0.191 g, 61.1% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.98-1.55 (4H, m), 2.96 (3H, s), 3.03 (3H, s), 3.17-3.06 (1H, m), 3.60-3.43 (2H, m), 3.72-3.67 (1H, m), 4.08-3.99 (1H, m), 4.19 (2H, q), 4.28 (2H, s), 7.01 (1H, t), 7.32-7.26 (2H, m), 7.78-7.70 (3H, m), 8.48-8.46 (1H, m), 10.89 (1H, s); m/z (LC-MS, ESI+), RT=1.55 (M+H 467).

후처리

  1. customThe solvent was evaporated to dryness
  2. dissolutionthe gum was dissolved in acetonitrile (4 mL)
  3. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  4. additionFractions containing the desired compound
  5. customwere evaporated to dryness

출처 및 근거

ORD 기록
ord-c9664f3bb0bd48509096897907757726
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129380B2

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