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

HRID 1466745Notes

Reaction equation

HRID 1466745 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]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[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]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:35])[CH2:31][CH2:30]1)=[O:28]

Participants

6

Reactant 4

HCID 11915Phenylglyoxylic 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 573441191-(4-(2-Fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)-2-phenylethane-1,2-dioneYield 33.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one TFA salt (311 mg, 0.65 mmol), 2-oxo-2-phenylacetic acid (900 mg, 6 mmol), DIPEA (2 ml, 11.6 mmol), and HATU (1010 mg, 2.65 mmol) were mixed in DMF (50 ml), the resulting reaction mixture was stirred at room temperature for 4 days until the reaction finished (monitored by TLC). The reaction mixture was then partitioned between DCM and water (100 ml each, the water phase was extracted with DCM (100 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 firstly purified by column chromatography on silica gel (DCM:MeOH=100:1) and re-purified by preparative TLC (DCM:MeOH=40:1) to afford the desired product (110 mg, 32.9%) as an off white 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 (100 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 firstly purified by column chromatography on silica gel (DCM:MeOH=100:1)
  10. customre-purified by preparative TLC (DCM:MeOH=40:1)

Sources & evidence

ORD record
ord-176458d35a4c4c079ce70443287a4de2
Source dataset
uspto-grants-2015_04
Patent number
US08999985B2

Reaction notes

Loading…