Bromobenzene → 5-(3-fluoro-4-methoxyphenyl)-N-phenylpyrimidin-2-amine

HRID 1993353Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[N:12][C:13]([NH2:16])=[N:14][CH:15]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].Br[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[N:14][C:13]([NH:16][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Participants

Conditions

Temperature: 200 °C

Procedure

A mixture of 5-(3-fluoro-4-methoxyphenyl)pyrimidin-2-amine (Step 1, 0.44 g, 2.0 mmol) and bromobenzene (0.60 g, 4.0 mmol) in N,N′-dimethylacetamide (1.0 mL) and toluene (1.0 mL) was placed in a microwave tube and was treated with Pd(OAc)2 (0.024 g, 0.1 mmol), 2-biscyclohexyl 1,1-biphenyl phosphine (Strem Chemical, 0.070 g, 0.20 mmol), and KOtBu (0.44 g, 4.0 mmol). The mixture was degassed with N2 (2×) and was subject to microwave heating at 200° C. for a total of 20 min. After the mixture was cooled to RT, it was filtered through a pad of Celite®. The solid was washed with EtOAc (3×10 mL), and the combined organic phase was washed with H2O, NH4Cl (sat.), dried with Na2SO4, and concentrated to an oil. Purification on silica using hexanes-EtOAc (3:1) resulted the desired compound as a yellow solid. MS (ESI pos. ion) m/z: 296. Calc'd for C17H14FN3O: 295.11.

Workup

customwas placed in a microwave tube
customThe mixture was degassed with N2 (2×)
temperatureAfter the mixture was cooled to RT
filtrationit was filtered through a pad of Celite®
washThe solid was washed with EtOAc (3×10 mL)
washthe combined organic phase was washed with H2O, NH4Cl (sat.)
dry with materialdried with Na2SO4
concentrationconcentrated to an oil
customPurification on silica

Sources & evidence

ORD record: ord-174c86706a9b45e39020fbeac83a63eb
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07652009B2

Reaction notes

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