Diisopropylethylamine → HCID 57791767, compound

HRID 1091773Notes

Reaction equation

HRID 1091773 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](O)=[O:5].[CH3:23][O:24][CH2:25][C@@H:26]([O:28][CH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)[CH3:27].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:32]1[CH2:33][CH2:34][CH:29]([O:28][C@@H:26]([CH3:27])[CH2:25][O:24][CH3:23])[CH2:30][CH2:31]1)=[O:5]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 248117402-Fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acidHCID 57791794HCID 57791794, compound

Product 1

HCID 57791767HCID 57791767, compoundYield 70.7%

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), (S)-4-(1-methoxypropan-2-yloxy)piperidine (92) (0.151 g, 0.87 mmol) and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (0.280 g, 0.87 mmol) were dissolved in DMF (10 mL), to this was added DIPEA (0.152 mL, 0.87 mmol) and the reaction was stirred for 1 hour. The solvent was evaporated to dryness and the gum was dissolved in acetonitrile (4 mL) and 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 compound as a white foam; (0.215 g, 70.7% yield) 1H NMR (400.132 MHz, CDCl3) δ 1.13 (3H, t), 1.61-1.49 (1H, m), 1.78-1.65 (2H, m), 1.91-1.87 (1H, m), 3.17-3.01 (1H, m), 3.31-3.27 (1H, m), 3.39-3.35 (4H, m), 3.57-3.45 (2H, m), 3.72-3.67 (2H, m), 4.06-3.97 (1H, m), 4.27 (2H, s), 7.01 (1H, t), 7.31-7.26 (2H, m), 7.79-7.70 (3H, m), 8.49-8.45 (1H, m), 10.50 (1H, s); m/z (LC-MS, ESI+), RT=1.81 (M+H 454).

Workup

  1. customThe solvent was evaporated to dryness
  2. dissolutionthe gum was dissolved in acetonitrile (4 mL)
  3. custompurified 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-c99e3dab5816421092f127822c041f24
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

Loading…