Diisopropylethylamine → 4-[[3-[3-(difluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]-4-fluoro-phenyl]methyl]-2H-phthalazin-1-one

HRID 920991Notes

Reaction equation

HRID 920991 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[F:47][CH:48]([F:58])[C:49]1[N:53]2[CH2:54][CH2:55][NH:56][CH2:57][C:52]2=[N:51][N:50]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[F:58][CH:48]([F:47])[C:49]1[N:53]2[CH2:54][CH2:55][N:56]([C:4]([C:3]3[CH:7]=[C:8]([CH2:11][C:12]4[C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[C:15](=[O:22])[NH:14][N:13]=4)[CH:9]=[CH:10][C:2]=3[F:1])=[O:6])[CH2:57][C:52]2=[N:51][N:50]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 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 acidHCID 625871663-(difluoromethyl)-5H,6H,7H,8H-(1,2,4)triazolo(4,3-a)pyrazine

Product 1

HCID 568326884-[[3-[3-(difluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]-4-fluoro-phenyl]methyl]-2H-phthalazin-1-oneYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoic acid 1a (685 mg, 2.30 mmol) was dissolved in 10 mL of N,N-dimethylformamide, followed by addition of O-(1-benzotriazolyl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.10 g, 3.45 mmol), crude 3-(difluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine 23d (400 mg, 2.30 mmol) and N,N-diisopropylethylamine (1.2 mL, 6.90 mmol). After stirring for 12 hours, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by thin layer chromatography with elution system A to obtain 4-[[3-[3-(difluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]-4-fluoro-phenyl]methyl]-2H-phthalazin-1-one 23 (200 mg, yield 20.0%) as a white solid.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. customthe resulting residue was purified by thin layer chromatography with elution system

Sources & evidence

ORD record
ord-d9811a7d84004386be728f94bb530745
Source dataset
uspto-grants-2016_03
Patent number
US09273052B2

Reaction notes

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