Triethylamine → 4-{[4-Fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl]methyl}phthalazin-1(2H)-one

HRID 1091812Notes

Reaction equation

HRID 1091812 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[F:25][C:26]1[CH:34]=[CH:33][C:32]([CH2:35][C:36]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:39](=[O:46])[NH:38][N:37]=2)=[CH:31][C:27]=1[C:28](O)=[O:29].[CH3:47][O:48][CH:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1.C(N(CC)CC)C>CC(N(C)C)=O.O>[F:25][C:26]1[CH:34]=[CH:33][C:32]([CH2:35][C:36]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:39](=[O:46])[NH:38][N:37]=2)=[CH:31][C:27]=1[C:28]([N:52]1[CH2:53][CH2:54][CH:49]([O:48][CH3:47])[CH2:50][CH2:51]1)=[O:29]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 776664-MethoxypiperidineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 248117402-Fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acid

Product 1

HCID 441993174-{[4-Fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl]methyl}phthalazin-1(2H)-oneYield 61.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
20 °C

Procedure

O-Benzotriazol-1-yl-tetramethyluronium hexafluorophosphate (45.5 g, 119.86 mmol) was added portionwise to a solution of 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (27.5 g, 92.20 mmol), 4-methoxypiperidine (11.68 g, 101.42 mmol) and triethylamine (30.8 mL, 221.28 mmol) in DMA (450 mL) at 20° C. under nitrogen. The resulting solution was stirred at 20° C. for 21 hours. The solution was poured into water (2.5 liters) and extracted with EtOAc (×3), the combined extracts washed with brine (×3), dried (MgSO4), filtered and evaporated to a gum. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness and slurried with EtOAc to afford 4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one (2b) (22.45 g, 61.6%) as a white solid after filtration and vacuum drying.

Workup

  1. extractionextracted with EtOAc (×3)
  2. washthe combined extracts washed with brine (×3)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated to a gum
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-a3741a261f3f45cbbde593a52923f82f
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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