2-Methoxy-5-(trifluoromethoxy)phenylboronic acid → (3-(2-Methoxy-5-trifluoromethoxyphenyl)-6-chloropyrazin-2-yl)[(4-methoxyphenyl)methyl]amine

HRID 349189Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10]([F:13])([F:12])[F:11])=[CH:5][C:4]=1B(O)O.Br[C:18]1[N:19]=[CH:20][C:21]([NH:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)=[N:22][C:23]=1[Cl:24]>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10]([F:13])([F:12])[F:11])=[CH:5][C:4]=1[C:20]1[C:21]([NH:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)=[N:22][C:23]([Cl:24])=[CH:18][N:19]=1

Participants

Conditions

Temperature: 80 °C

Procedure

In a pressure tube, a mixture of the product from step A (1 equivalent), 2-methoxy-5-trifluoromethoxyphenylboronic acid (1.6 equivalents) and Pd(PPh3)4 (0.04 equivalents) in toluene (4 ml/mmol of product from step A), ethanol (0.2 ml/mmol of product from step A) and aqueous K2CO3 (2M, 2 ml/mmol of product from step A) is heated to 80° C. for 16 hours. The mixture is diluted with ethyl acetate, and the organic fraction washed with NaOH (2M, 20 mL/mmol of product from step A) and brine (3×20 ml/mmol of product from step A), then dried (MgSO4), filtered and the solvent removed under reduced pressure. Chromatography of the residue provides (3-(2-methoxy-5-trifluoromethoxyphenyl)-6-chloropyrazin-2-yl)[(4-methoxyphenyl)methyl]amine.

Workup

washthe organic fraction washed with NaOH (2M, 20 mL/mmol of product from step A) and brine (3×20 ml/mmol of product from step A)
dry with materialdried (MgSO4)
filtrationfiltered
customthe solvent removed under reduced pressure

Sources & evidence

ORD record: ord-9cb60699dccd40079667ca47657d1c3a
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07179807B2

Reaction notes

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