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

HRID 1441632Notes

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].[CH3:17][N:18]1[C:22]([Sn](CCCC)(CCCC)CCCC)=[CH:21][CH:20]=[N:19]1>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:22]2[N:18]([CH3:17])[N:19]=[CH:20][CH:21]=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 (0.80 g, 2.35 mmol) in dioxane (10 mL) were added 1-methyl-5-tributylstannanyl-1H-pyrazole (1.05 g, 2.81 mmol) and Pd(PPh3)2Cl2 (168 mg, 0.235 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-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (430 mg, 1.46 mmol, 62%). ES-MS: m/z 296 [M+H]+, rt 6.05 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-0939d8afcc044eb2be1cfc17a7956c7a
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07655666B2

Reaction notes

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