Methyl 2-amino-4-(1,1-difluoroethyl)-5-iodobenzoate → 2-amino-4-(1,1-difluoro-ethyl)-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester

HRID 906607Notes

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])[CH3:12])=[CH:6][C:5]=1[NH2:15].[CH:17]([N:20]1[C:24]([Sn](CCCC)(CCCC)CCCC)=[CH:23][CH:22]=[N:21]1)([CH3:19])[CH3:18]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([C:24]2[N:20]([CH:17]([CH3:19])[CH3:18])[N:21]=[CH:22][CH:23]=2)[C:7]([C:11]([F:14])([F:13])[CH3:12])=[CH:6][C:5]=1[NH2:15]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 2-amino-4-(1,1-difluoro-ethyl)-5-iodo-benzoic acid methyl ester (0.809 g, 2.37 mmol) in dioxane (10 mL) were added 1-isopropyl-5-tributylstannanyl-1H-pyrazole (1.14 g, 2.84 mmol) and Pd(PPh3)2Cl2 (170 mg, 0.237 mmol) and the resulting mixture was stirred at 90° C. for 72 h. The solvent was removed in vacuo to afford a dark oil. The crude product was purified by flash chromatography (silica gel, EtOAc/hexanes (0:10 to 3:7)) to give 2-amino-4-(1,1-difluoro-ethyl)-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (141 mg, 0.436 mmol, 18%) ES-MS: m/z 324 [M+H]+, rt 6.39 min.

Workup

customThe solvent was removed in vacuo
customto afford a dark oil
customThe crude product was purified by flash chromatography (silica gel, EtOAc/hexanes (0:10 to 3:7))

Sources & evidence

ORD record: ord-2a1dec7cd5fc4ac8a78157a81eb77835
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012988B2

Reaction notes

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