Pyruvic Acid → 1-(4-(2-Fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)propane-1,2-dione

HRID 1466752Notes

Reaction equation

HRID 1466752 reaction equation
OC(C(F)(F)F)=O.[F:8][C:9]1[CH:26]=[CH:25][C:12]([CH2:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17](=[O:24])[NH:16][N:15]=2)=[CH:11][C:10]=1[C:27]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)=[O:28].[O:35]=[C:36]([CH3:40])[C:37](O)=[O:38].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:8][C:9]1[CH:26]=[CH:25][C:12]([CH2:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17](=[O:24])[NH:16][N:15]=2)=[CH:11][C:10]=1[C:27]([N:29]1[CH2:34][CH2:33][N:32]([C:37](=[O:38])[C:36](=[O:35])[CH3:40])[CH2:31][CH2:30]1)=[O:28]

Participants

6

Reactant 4

HCID 1060Pyruvic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 865830904-(4-Fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one 2,2,2-trifluoroacetate

Product 1

HCID 573441251-(4-(2-Fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)propane-1,2-dioneYield 13.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one TFA salt (157.5 mg, 0.34 mmol), 2-oxopropanoic acid (0.15 ml (d=1.26), 2.15 mmol), DIPEA (0.5 ml, 3 mmol), and HATU (258.6 mg, 0.68 mmol) were mixed in DMF (20 ml), the resulting reaction mixture was stirred at room temperature for 60 h until the reaction finished (monitored by TLC). The reaction mixture was then partitioned between DCM and water (50 ml each, the water phase was extracted with DCM (50 ml). The combined organic phase was washed with water, sat. aqueous sodium bicarbonate, and brine, dried over sodium sulphate, filtered, and concentrated to yield the crude product. Then the crude product was purified by column chromatography on silica gel (Petroleum ether: Ethyl Acetate=1:2) to afford the desired product (20 mg, 13.5%) as a light yellow solid.

Workup

  1. customthe resulting reaction mixture
  2. customThe reaction mixture was then partitioned between DCM and water (50 ml each
  3. extractionthe water phase was extracted with DCM (50 ml)
  4. washThe combined organic phase was washed with water, sat. aqueous sodium bicarbonate, and brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield the crude product
  9. customThen the crude product was purified by column chromatography on silica gel (Petroleum ether: Ethyl Acetate=1:2)

Sources & evidence

ORD record
ord-d8b653b943ac48cc823d6464a40211c2
Source dataset
uspto-grants-2015_04
Patent number
US08999985B2

Reaction notes

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