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

HRID 1091764Notes

Reaction equation

HRID 1091764 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-c9664f3bb0bd48509096897907757726
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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