Methylhydrazine → 3-(3-chlorophenyl)-1-methyl-1H-pyrazol-4-amine

HRID 1466569Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:8](=O)[C:9]([N:14]2C(=O)C3C(=CC=CC=3)C2=O)=[CH:10][N:11](C)[CH3:12])[CH:5]=[CH:6][CH:7]=1.C[NH:27]N>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]([NH2:14])=[CH:10][N:11]([CH3:12])[N:27]=2)[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 2-(3-(3-chlorophenyl)-1-(dimethylamino)-3-oxoprop-1-en-2-yl)isoindoline-1,3-dione (2.30 g, 6.48 mmol, 1 eq) in 50 mL ethanol was added N-methylhydrazine (1.4 mL, 26 mmol, 4.0 eq). The reaction mixture was stirred at 80° C. for 2 hours and then concentrated onto silica gel. The crude mixture of regioisomers was separated and purified by flash chromatography on silica gel (0 to 80% ethyl acetate in dichloromethane) to yield: 715 mg (53%) of 3-(3-chlorophenyl)-1-methyl-1H-pyrazol-4-amine LCMS (ESI) m+H=208.2; 1H NMR (400 MHz, CDCl3) δ: 7.78 (s, 1H), 7.63 (d, 1H), 7.33 (t, 1H), 7.25 (overlapping with CDCl3, 1H), 7.04 (s, 1H), 3.84 (s, 3H), and 274.6 mg (20%) of 5-(3-chlorophenyl)-1-methyl-1H-pyrazol-4-amine. LCMS (ESI) m+H=208.2; 1H NMR (400 MHz, CDCl3) δ: 7.43 (t, 1H), 7.38 (overlapping d and s, 2H), 7.27 (d, 1H), 7.23 (s, 1H), 3.76 (s, 3H).

Workup

concentrationconcentrated onto silica gel
additionThe crude mixture of regioisomers
customwas separated
custompurified by flash chromatography on silica gel (0 to 80% ethyl acetate in dichloromethane) to yield: 715 mg (53%) of 3-(3-chlorophenyl)-1-methyl-1H-pyrazol-4-amine LCMS (ESI) m+H=208.2

Sources & evidence

ORD record: ord-687663823657483384a812440f7cf025
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999998B2

Reaction notes

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