4-Methoxypiperidine → 4-(4-Fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-5-methoxyphthalazin-1(2h)-one

HRID 1091806Notes

Reaction equation

HRID 1091806 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][C:20]=3[O:22][CH3:23])[C:15](=[O:24])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4](O)=[O:5].[CH3:25][O:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>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][C:20]=3[O:22][CH3:23])[C:15](=[O:24])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([N:30]1[CH2:31][CH2:32][CH:27]([O:26][CH3:25])[CH2:28][CH2:29]1)=[O:5]

Participants

6

Reactant 4

HCID 776664-MethoxypiperidineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 577918172-Fluoro-5-[(8-methoxy-4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acid

Product 1

HCID 665933194-(4-Fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-5-methoxyphthalazin-1(2h)-oneYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-fluoro-5-((8-methoxy-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (125) and 4-methoxypiperidine were added to DMF (5 mL), to this was added N-ethyl-N-isopropylpropan-2-amine (0.163 mL, 0.91 mmol) and then HBTU (347 mg, 0.91 mmol). The solvent was removed and the residue was dissolved in acetonitrile. A white solid precipitated, which was filtered and dried to afford the desired material as a white crystalline solid (140 mg, 54.0% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.49-1.60 (1H, m), 1.62-1.83 (2H, m), 1.86-1.96 (1H, m), 3.07-3.19 (1H, m), 3.32-3.36 (3H, m), 3.41-3.62 (3H, m), 3.78-3.82 (3H, m), 3.94-4.04 (1H, m), 4.36-4.46 (2H, m), 6.93-7.00 (1H, m), 7.10-7.30 (3H, m), 7.64-7.72 (1H, m), 8.00-8.12 (1H, m), 9.98-10.07 (1H, m); m/z (ES+) (M+H)+=426.4; HPLC RT=1.71 min.

Workup

  1. customThe solvent was removed
  2. dissolutionthe residue was dissolved in acetonitrile
  3. customA white solid precipitated
  4. filtrationwhich was filtered
  5. customdried

Sources & evidence

ORD record
ord-15a5108275fe41988e501ad4fd6233a4
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

Loading…