Diisopropylethylamine → N-(cyclopropylmethyl)-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

HRID 920995Notes

Reaction equation

HRID 920995 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.[CH:47]1([CH2:50][NH:51][C:52]([C:54]2[N:55]=[C:56]([C:63]([F:66])([F:65])[F:64])[N:57]3[CH2:62][CH2:61][NH:60][CH2:59][C:58]=23)=[O:53])[CH2:49][CH2:48]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH:47]1([CH2:50][NH:51][C:52]([C:54]2[N:55]=[C:56]([C:63]([F:64])([F:65])[F:66])[N:57]3[CH2:62][CH2:61][N:60]([C:4](=[O:5])[C:3]4[CH:7]=[C:8]([CH2:11][C:12]5[C:21]6[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=6)[C:15](=[O:22])[NH:14][N:13]=5)[CH:9]=[CH:10][C:2]=4[F:1])[CH2:59][C:58]=23)=[O:53])[CH2:49][CH2:48]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 68011901N-(cyclopropylmethyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide

Product 1

HCID 56832734N-(cyclopropylmethyl)-7-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]-3-(trifluoromethyl)-6,8-dihydro-5H-imidazo[1,5-a]pyrazine-1-carboxamideYield 30.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoic acid 1a (300 mg, 1 mmol) was dissolved in 5 mL of N,N-dimethylformamide, followed by addition of O-(1-benzotriazolyl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (756 mg, 2 mmol), crude N-(cyclopropylmethyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide 24c (250 mg, 0.87 mmol) and N, N-diisopropylethylamine (0.5 mL, 3 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 N-(cyclopropylmethyl)-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 24 (150 mg, yield 30.0%) as a light yellow 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-edd2be66cbb6432abd03517b2542662a
Source dataset
uspto-grants-2016_03
Patent number
US09273052B2

Reaction notes

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