1,2,4-Trifluoro-5-nitrobenzene → 5-cyclopropyl-N-(4,5-difluoro-2-nitrophenyl)-1H-pyrazol-3-amine

HRID 1092236Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5](F)=[CH:4][C:3]=1[F:12].CCN(C(C)C)C(C)C.[CH:22]1([C:25]2[NH:29][N:28]=[C:27]([NH2:30])[CH:26]=2)[CH2:24][CH2:23]1>C1COCC1>[CH:22]1([C:25]2[NH:29][N:28]=[C:27]([NH:30][C:5]3[CH:4]=[C:3]([F:12])[C:2]([F:1])=[CH:7][C:6]=3[N+:8]([O-:10])=[O:9])[CH:26]=2)[CH2:24][CH2:23]1

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of 1,2,4-trifluoro-5-nitrobenzene (3.0 g, 18 mmol) and DIEA (4.2 ml, 24 mmol) in dry THF (20 ml) was added dropwise a solution of 5-cyclopropyl-1H-pyrazol-3-amine (2.0 g, 16 mmol) in THF (5 ml) at 0° C. After addition, the reaction mixture was stirred at 25° C. for 20 hrs. It was then heated to 40° C. for 40 hrs. The solvent was removed under reduced pressure and the resulted residue was purified by column chromatography (hexane:EtOAc=5:2). Recrystallization from EtOAc (10 ml) and hexanes (˜100 ml) gave the title compound as red crystals (0.8 g, 18%). NMR (400 MHz) 12.36 (s, 1H), 9.79 (s, 1H), 8.27 (m, 2H), 5.93 (s, 1H), 1.90 (m, 1H), 0.93 (m, 2H), 0.72 (m, 2H). MS: Calcd.: 280; Found: [M+H]+ 281.

Workup

additionAfter addition
temperatureIt was then heated to 40° C. for 40 hrs
customThe solvent was removed under reduced pressure
customthe resulted residue was purified by column chromatography (hexane:EtOAc=5:2)
customRecrystallization from EtOAc (10 ml) and hexanes (˜100 ml)

Sources & evidence

ORD record: ord-3f568f3f45ce41c99296e08729a38036
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129403B2

Reaction notes

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