2-Amino-4-difluoromethyl-5-iodo-benzoic acid methyl ester → 2-Amino-4-difluoromethyl-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester

HRID 906596Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8](I)[C:7]([CH:11]([F:13])[F:12])=[CH:6][C:5]=1[NH2:14].[CH:16]([N:19]1[C:23]([Sn](CCCC)(CCCC)CCCC)=[CH:22][CH:21]=[N:20]1)([CH3:18])[CH3:17]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([C:23]2[N:19]([CH:16]([CH3:18])[CH3:17])[N:20]=[CH:21][CH:22]=2)[C:7]([CH:11]([F:13])[F:12])=[CH:6][C:5]=1[NH2:14]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 2-amino-4-difluoromethyl-5-iodo-benzoic acid methyl ester (750 mg, 2.29 mmol) in dioxane (30 mL) were added 1-isopropyl-5-tributylstannanyl-1H-pyrazole (1.1 g, 1.2 equiv) and Pd(dppf)2Cl2 (187 mg, 0.1 equiv) and the resulting mixture was stirred at 90° C. for 18 h. Another portion of catalyst (0.1 equiv) was added and the mixture was stirred at 90° C. for an additional 6 h. The solvent was removed in vacuo to afford a dark oil. The crude product was purified by flash chromatography (silica gel, EtOAc/hexanes (0:100 to 30:70)) to provide the title compound as an off-white solid (380 mg, 54%). ES-MS: m/z 310.3 [M+H]+, rt 5.54 min.

Workup

stirringthe mixture was stirred at 90° C. for an additional 6 h
customThe solvent was removed in vacuo
customto afford a dark oil
customThe crude product was purified by flash chromatography (silica gel, EtOAc/hexanes (0:100 to 30:70))

Sources & evidence

ORD record: ord-d4a233ee4c5146daba7256badbfc6a64
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012988B2

Reaction notes

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