4-Methoxypiperidine → 5-chloro-4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one

HRID 1091784Notes

Reaction equation

HRID 1091784 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10]([CH2:12][C:13]1[CH:14]=[CH:15][C:16]([F:22])=[C:17]([CH:21]=1)[C:18](O)=[O:19])=[N:9][NH:8][C:7]2=[O:23].[CH3:24][O:25][CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10]([CH2:12][C:13]1[CH:14]=[CH:15][C:16]([F:22])=[C:17]([C:18]([N:29]3[CH2:30][CH2:31][CH:26]([O:25][CH3:24])[CH2:27][CH2:28]3)=[O:19])[CH:21]=1)=[N:9][NH:8][C:7]2=[O:23]

Participants

5

Reactant 3

HCID 776664-MethoxypiperidineHCID 81531DiisopropylethylamineHCID 57791854HCID 57791854, compound

Product 1

HCID 577918615-chloro-4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-oneYield 38.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-((8-chloro-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)-2-fluorobenzoic acid (103) (0.2 g, 0.60 mmol), 4-methoxypiperidine (0.069 g, 0.60 mmol) and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (0.251 g, 0.78 mmol) were dissolved in DMF (10 mL), to this was added DIPEA (0.136 mL, 0.78 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 material as a white foam (0.100 g, 38.7%); 1H NMR (400.132 MHz, CDCl3) δ 1.60-1.49 (1H, m), 1.83-1.64 (2H, m), 1.94-1.89 (1H, m), 3.17-3.05 (1H, m), 3.35 (3H, s), 3.48-3.44 (2H, m), 3.61-3.48 (1H, m), 4.03-3.93 (1H, m), 4.65 (2H, s), 7.00 (1H, t), 7.17-7.14 (2H, m), 7.66 (1H, t), 7.80 (1H, dd), 8.49 (1H, dd) NH missing; m/z (LC-MS, ESI+), RT=1.89 (M+H 430).

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-0b74c6f325374c878a430b4d9e6fea7f
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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