Diisopropylethylamine → 1-Cyclopropyl-2-(4-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl) piperazin-1-yl)ethane-1,2-dione

HRID 1466741Notes

Reaction equation

HRID 1466741 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].[CH:35]1([C:38](=[O:42])[C:39](O)=[O:40])[CH2:37][CH2:36]1.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>[CH:35]1([C:38](=[O:42])[C:39]([N:32]2[CH2:33][CH2:34][N:29]([C:27](=[O:28])[C:10]3[CH:11]=[C:12]([CH2:13][C:14]4[C:23]5[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=5)[C:17](=[O:24])[NH:16][N:15]=4)[CH:25]=[CH:26][C:9]=3[F:8])[CH2:30][CH2:31]2)=[O:40])[CH2:37][CH2:36]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 122119382-Cyclopropyl-2-oxoacetic acidHCID 865830904-(4-Fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one 2,2,2-trifluoroacetate

Product 1

HCID 573441171-Cyclopropyl-2-(4-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl) piperazin-1-yl)ethane-1,2-dioneYield 49.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one TFA salt (1.24 g, 2.68 mmol), 2-cyclopropyl-2-oxoacetic acid (2.84 g, 24.84 mmol), DIPEA (6.9 ml, 41.4 mmol), and HATU (4.08 g, 10.8 mmol) were mixed in DMF (100 ml), the resulting reaction mixture was stirred at room temperature for overnight 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 purified by column chromatography on silica gel (DCM: MeOH=100:1) and re-crystallized from methanol to afford the desired product (610 mg, 49.3%) as a 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 purified by column chromatography on silica gel (DCM: MeOH=100:1)
  10. customre-crystallized from methanol

Sources & evidence

ORD record
ord-bc2c7b9cd4ac45e2ab79dde305b07c2b
Source dataset
uspto-grants-2015_04
Patent number
US08999985B2

Reaction notes

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