2-Furylglyoxylic acid → 1-(4-(2-Fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)-2-(furan-2-yl)ethane-1,2-dione

HRID 1466750Notes

Reaction equation

HRID 1466750 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]1[CH:39]=[CH:38][CH:37]=[C:36]1[C:40](=[O:44])[C:41](O)=[O:42].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:41](=[O:42])[C:40]([C:36]2[O:35][CH:39]=[CH:38][CH:37]=2)=[O:44])[CH2:31][CH2:30]1)=[O:28]

Participants

6

Reactant 4

HCID 738462-Furylglyoxylic 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 573441241-(4-(2-Fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)-2-(furan-2-yl)ethane-1,2-dioneYield 20.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one TFA salt (155 mg, 0.32 mmol), 2-(furan-2-yl)-2-oxoacetic acid (278 mg, 1.98 mmol), DIPEA (0.5 ml, 3 mmol), and HATU (251 mg, 0.66 mmol) were mixed in DMF (30 ml), the resulting reaction mixture was stirred at room temperature for 45 h until the reaction finished (monitored by TLC). The reaction mixture was then partitioned between DCM and water (100 ml each, and 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=1:3) to afford the desired product (20 mg, 20.4%) as a light yellow solid.

Workup

  1. customthe resulting reaction mixture
  2. customThe reaction mixture was then partitioned between DCM and water (100 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=1:3)

Sources & evidence

ORD record
ord-91929331115247e1b9518bec22a414d3
Source dataset
uspto-grants-2015_04
Patent number
US08999985B2

Reaction notes

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