Methylamine → 5-Amino-1-(4-fluorophenyl)-4-[3-(methylaminocarbonylmethyloxy)benzoyl]pyrazole

HRID 489844Notes

Reaction equation

[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14](=[O:26])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][C:23]([OH:25])=O)[CH:16]=1.C(C1NC=CN=1)([C:29]1[NH:30]C=CN=1)=O.CN>O1CCCC1.C(OCC)(=O)C>[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14](=[O:26])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][C:23]([NH:30][CH3:29])=[O:25])[CH:16]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 5-amino-4-[3-(carboxymethyloxy)benzoyl]-1-(4-fluorophenyl)pyrazole (0.5 g, 1.43 mmol) in tetrahydrofuran (10 ml) was added carbonyl diimidazole (0.3 g, 1.85 mmol) and the reaction mixture was heated at 60° C. After 1 h, methylamine (10 ml, 5 mmol, 0.5 M solution in tetrahydrofuran) was added and reaction was continued at 60° C. overnight. The reaction mixture was cooled and diluted with ethyl acetate. The organic layer was separated and washed with brine and dried over sodium sulfate. The organics were removed in vacuo and the residue was purified by flash chromatography (elution gradient: 20-30% acetone/hexane) to give 5-amino-1-(4-fluorophenyl)-4-[3-(methylaminocarbonyl-methyloxy)benzoyl]pyrazole (0.25 g, mpt. 195.6-196.3° C.) as a solid.

Workup

customreaction
waitwas continued at 60° C. overnight
temperatureThe reaction mixture was cooled
customThe organic layer was separated
washwashed with brine
dry with materialdried over sodium sulfate
customThe organics were removed in vacuo
customthe residue was purified by flash chromatography (elution gradient: 20-30% acetone/hexane)

Sources & evidence

ORD record: ord-e4660d5fdf674197890709fb972bdd2a
Source dataset: uspto-grants-2005_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06979693B2

Reaction notes

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