Diisopropylethylamine → HCID 56832736, compound

HRID 920999Notes

Reaction equation

HRID 920999 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:60])([F:59])[CH2:49][C:50]1[N:54]2[CH2:55][CH2:56][NH:57][CH2:58][C:53]2=[N:52][N:51]=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:57]1[CH2:56][CH2:55][N:54]2[C:50]([CH2:49][C:48]([F:47])([F:59])[F:60])=[N:51][N:52]=[C:53]2[CH2:58]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 62588062837430-20-3

Product 1

HCID 56832736HCID 56832736, compoundYield 22.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoic acid 1a (801 mg, 2.69 mmol) was dissolved in 25 mL of N,N-dimethylformamide, followed by addition of O-(1-benzotriazolyl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.27 g, 3.36 mmol), crude 3-(2,2,2-trifluoro ethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine 26b (460 mg, 2.24 mmol) and N, N-diisopropylethylamine (0.8 mL, 4.48 mmol). After stirring for 12 hours, the reaction mixture was concentrated under reduced pressure, added with 30 mL of H2O and extracted with ethyl acetate (30 mL×3). The organic phase was combined, concentrated under reduced pressure, added with 30 mL of ethyl acetate, 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-[3-(2,2,2-trifluoroethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one 26 (240 mg, yield 22.1%) as a white solid.

Workup

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

Sources & evidence

ORD record
ord-6f8f18c6d0ff4e02841f8ed7ae6c4100
Source dataset
uspto-grants-2016_03
Patent number
US09273052B2

Reaction notes

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