Diisopropylethylamine → HCID 56833306, compound

HRID 920959Notes

Reaction equation

HRID 920959 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.[CH2:47]([NH:49][C:50]([C:52]1[N:53]=[C:54]([C:61]([F:64])([F:63])[F:62])[N:55]2[CH2:60][CH2:59][NH:58][CH2:57][C:56]=12)=[O:51])[CH3:48].C(N(CC)C(C)C)(C)C>CN(C)C=O.O>[CH2:47]([NH:49][C:50]([C:52]1[N:53]=[C:54]([C:61]([F:63])([F:64])[F:62])[N:55]2[CH2:60][CH2:59][N:58]([C:4](=[O:5])[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])[CH2:57][C:56]=12)=[O:51])[CH3:48]

Participants

7

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 68011884HCID 68011884, compound

Product 1

HCID 56833306HCID 56833306, compoundYield 43.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-Fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoic acid 1a (250 mg, 0.84 mmol) was dissolved in 20 mL of N,N-dimethylformamide, followed by addition of O-(1-benzotriazolyl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (480 mg, 1.26 mmol), crude N-ethyl-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide 7a (242 mg, 0.92 mmol) and N, N-diisopropylethylamine (0.3 mL, 1.68 mmol). After stirring for 12 hours, the reaction mixture was added with 50 mL of H2O, and extracted with dichloromethane (50 mL×3). The organic phase was combined, concentrated under reduced pressure, added with 100 mL of ethyl acetate, washed successively with saturated sodium bicarbonate solution (40 mL), saturated sodium chloride solution (40 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 N-ethyl-7-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]-3-(trifluoromethyl)-6,8-dihydro-5H-imidazo[1,5-a]pyrazine-1-carboxamide 7 (200 mg, yield 43.9%) as a white solid.

Workup

  1. extractionextracted with dichloromethane (50 mL×3)
  2. concentrationconcentrated under reduced pressure
  3. additionadded with 100 mL of ethyl acetate
  4. washwashed successively with saturated sodium bicarbonate solution (40 mL), saturated sodium chloride solution (40 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe resulting residue was purified by thin layer chromatography with elution system

Sources & evidence

ORD record
ord-860f766d27a94a85be872895499bc847
Source dataset
uspto-grants-2016_03
Patent number
US09273052B2

Reaction notes

Loading…