Diisopropylethylamine → 4-(3-(4-(2-(dimethylamino)ethoxy)piperidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one

HRID 1091767Notes

Reaction equation

HRID 1091767 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]([CH3:34])[CH2:25][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>[CH3:23][N:24]([CH3:34])[CH2:25][CH2:26][O:27][CH:28]1[CH2:33][CH2:32][N:31]([C:4]([C:3]2[CH:7]=[C:8]([CH:9]=[CH:10][C:2]=2[F:1])[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)=[O:6])[CH2:30][CH2:29]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 248117402-Fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acidHCID 43167826Dimethyl(2-(piperidin-4-yloxy)ethyl)amine

Product 1

HCID 577918554-(3-(4-(2-(dimethylamino)ethoxy)piperidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-oneYield 28.7%

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)ethanamine (85) (0.116 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 white solid (0.087 g, 28.7% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.62-1.51 (1H, m), 1.84-1.66 (3H, m), 1.95-1.89 (1H, m), 2.28 (6H, s), 2.52 (2H, t), 3.15-3.01 (1H, m), 3.48-3.40 (1H, m), 3.62-3.51 (3H, m), 4.07-3.98 (1H, m), 4.27 (2H, s), 7.01 (1H, t), 7.32-7.25 (2H, m), 7.77-7.70 (3H, m), 8.47-8.45 (1H, m), 10.62 (1H, s); m/z (LC-MS, ESI+), RT=1.67 (M+H 452).

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-c37055a9189746289f0b12aa5ab87261
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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