Methyl 2-amino-5-iodo-4-(trifluoromethyl)benzoate → 2-amino-5-(2,5-dimethyl-2H-pyrazol-3-yl)-4-trifluoromethyl-benzoic acid methyl ester

HRID 906549Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](I)[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[NH2:15].[CH3:17][N:18]1[C:22]([Sn](CCCC)(CCCC)CCCC)=[CH:21][C:20]([CH3:36])=[N:19]1>O1CCOCC1>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([C:22]2[N:18]([CH3:17])[N:19]=[C:20]([CH3:36])[CH:21]=2)[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[NH2:15]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture containing 2-amino-5-iodo-4-trifluoromethyl-benzoic acid methyl ester (1.0 g, 2.9 mmol), 1,3-dimethyl-5-tributylstannanyl-1H-pyrazole (1.34, 1.2 equiv) and bistriphenylphosphinedichloropalladium (207 mg, 0.1 equiv) in dioxane (15 mL) was stirred for 18 h at 80° C. Bistriphenylphosphinedichloropalladium (0.1 equiv) and another portion of the stannyl derivative (0.4 equiv) were added and the mixture was stirred for 24 h at 80° C. The mixture was evaporated to dryness. The crude product was purified by flash chromatography (hexanes to EtOAc/hexanes (1:1)) to provide 2-amino-5-(2,5-dimethyl-2H-pyrazol-3-yl)-4-trifluoromethyl-benzoic acid methyl ester (651 mg, 72%) as a yellow paste. (ESI-MS: m/z 314.2 [M+H]+, rt 5.12 min).

Workup

stirringthe mixture was stirred for 24 h at 80° C
customThe mixture was evaporated to dryness
customThe crude product was purified by flash chromatography (hexanes to EtOAc/hexanes (1:1))

Sources & evidence

ORD record: ord-efd128f3ad954b318ea3bc2de5cefbd3
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012988B2

Reaction notes

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