Diisopropylethylamine → Fuzuloparib

HRID 920978Notes

Reaction equation

HRID 920978 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](O)=[O:5].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[F:47][C:48]([F:59])([F:58])[C:49]1[N:57]=[C:52]2[CH2:53][NH:54][CH2:55][CH2:56][N:51]2[N:50]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[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]([N:54]1[CH2:55][CH2:56][N:51]2[N:50]=[C:49]([C:48]([F:58])([F:47])[F:59])[N:57]=[C:52]2[CH2:53]1)=[O:5]

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 341763295,6,7,8-Tetrahydro-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrazine

Product 1

HCID 56649297FuzuloparibYield 16.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoic acid 1a (780 mg, 2.65 mmol) was dissolved in 15 mL of N,N-dimethylformamide, followed by addition of O-(1-benzotriazolyl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.80 g, 4.77 mmol), 2-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine 19a (560 mg, 2.92 mmol, prepared according to a known method disclosed by “patent application WO2009025784”) and N,N-diisopropylethylamine (1.4 mL, 7.95 mmol). After stirring for 12 hours, the reaction mixture was concentrated under reduced pressure, added with 30 mL of H2O, extracted with ethyl acetate (30 mL×3). The organic phase was combined, washed with saturated sodium chloride solution (20 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by thin layer chromatography with elution system A to obtain 4-[[4-fluoro-3-[2-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[1,5-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one 19 (205 mg, yield 16.4%) as a light yellow solid.

Workup

  1. customprepared
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. additionadded with 30 mL of H2O
  4. extractionextracted with ethyl acetate (30 mL×3)
  5. washwashed with saturated sodium chloride solution (20 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe resulting residue was purified by thin layer chromatography with elution system

Sources & evidence

ORD record
ord-5de7c4a36e354022a0caf30e0b21c42e
Source dataset
uspto-grants-2016_03
Patent number
US09273052B2

Reaction notes

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