Methacrylamide → (E)-3-(3-(5-amino-3-(2-fluorophenyl)-1H-pyrazol-1-yl)phenyl)-2-methylacrylamide

HRID 1696591Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:12]=[C:11]([NH2:13])[N:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16](I)[CH:15]=2)[N:9]=1.[C:21]([NH2:26])(=[O:25])[C:22]([CH3:24])=[CH2:23].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC>CN(C=O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:13][C:11]1[N:10]([C:14]2[CH:15]=[C:16](/[CH:23]=[C:22](\[CH3:24])/[C:21]([NH2:26])=[O:25])[CH:17]=[CH:18][CH:19]=2)[N:9]=[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH:12]=1

Participants

Conditions

Temperature: 80 °C

Procedure

3-(2-Fluorophenyl)-1-(3-iodophenyl)-1H-pyrazol-5-amine (0.500 g, 1.32 mmol, 1.00 eq), methacrylamide (0.281 g, 3.30 mmol, 2.50 eq), Pd(OAc)2 (0.0118 g, 0.0527 mmol, 0.04 eq), Ph3P (0.0346 g, 0.132 mmol, 0.10 eq) and Et3N (0.919 ml, 6.59 (mmol, 5.00 eq) were combined in DMF (3 ml) and heated at 80° C. overnight. The reaction was cooled to RT, diluted with H2O and extracted with EtOAc (2×). The combined organics were washed with 5% citric acid (2×), brine (1×) and dried (MgSO4). Filtration and evaporation gave crude product which was purified by flash chromatography to afford 0.4192 g (95%) of pure (E)-3-(3-(5-amino-3-(2-fluorophenyl)-1H-pyrazol-1-yl)phenyl)-2-methylacrylamide. MS (ESI) m/z: 337.2 (M+H+).

Workup

temperatureThe reaction was cooled to RT
extractionextracted with EtOAc (2×)
washThe combined organics were washed with 5% citric acid (2×), brine (1×)
dry with materialdried (MgSO4)
filtrationFiltration and evaporation
customgave crude product which
customwas purified by flash chromatography

Sources & evidence

ORD record: ord-30c7ffdd97714068b5823360bdcc3e36
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163756B2

Reaction notes

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