3-Fluoroaniline → 4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-[1-methyl-2-(methylthio)ethyl]-2-pyrimidinamine

HRID 913290Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][CH:15]([CH3:19])[CH2:16][S:17][CH3:18])[N:9]=2)[CH:5]=[CH:4][N:3]=1.[F:20][C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][CH:27]=1)[NH2:24].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:20][C:21]1[CH:22]=[C:23]([NH:24][C:2]2[CH:7]=[C:6]([C:8]3[CH:13]=[CH:12][N:11]=[C:10]([NH:14][CH:15]([CH3:19])[CH2:16][S:17][CH3:18])[N:9]=3)[CH:5]=[CH:4][N:3]=2)[CH:25]=[CH:26][CH:27]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 4-(2-chloro-4-pyridinyl)-N-[1-methyl-2-(methylthio)ethyl]-2-pyrimidinamine (i.e., the product of Step C) (150 mg, 0.5 mmol) in toluene (6.0 mL) was added 3-fluoroaniline (108 μL, 1.1 mmol), palladium(II) acetate (24 mg, 0.12 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene ((±)-BINAP) (40 mg, 0.06 mmol) and cesium carbonate (700 mg, 2.2 mmol); the resulting mixture was stirred at 110° C. for 13 h. The mixture was allowed to cool and silica gel (300 mg) was added. The excess solvent was removed under reduced pressure, and the resulting solid was chromatographed on silica gel eluted with 5% to 60% ethyl acetate in hexanes to give 60 mg of the title compound as a yellow solid, m.p. 104-107° C.

Workup

temperatureto cool
additionsilica gel (300 mg) was added
customThe excess solvent was removed under reduced pressure
customthe resulting solid was chromatographed on silica gel
washeluted with 5% to 60% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-1c165ee1b2534e5dbcda429e26298761
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026359B2

Reaction notes

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