Cesium carbonate → 4-[4-(4-Iodo-2,6-dimethylphenoxy)pyrimidin-2-ylamino]benzonitrile

HRID 1893144Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)[N:3]=1.[I:17][C:18]1[CH:23]=[C:22]([CH3:24])[C:21]([OH:25])=[C:20]([CH3:26])[CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O.CCCCCC>[I:17][C:18]1[CH:23]=[C:22]([CH3:24])[C:21]([O:25][C:2]2[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]3[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=3)[N:3]=2)=[C:20]([CH3:26])[CH:19]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 4-(4-chloro-pyrimidin-2-ylamino)benzonitrile (Ludovici, et al. ibid) 2 (600.0 mg, 2.60 mmol), 4-iodo-2,6-dimethylphenol (Chabrier, et al., Ibid) (838.0 mg, 3.38 mmol) and cesium carbonate (2.20 g, 6.76 mmol) in dry DMF (12 mL) was heated to 90° C. (Zhang, et al., Tetrahedron Lett., 2002, 43, 8235-8239). After 3 hours, TLC (EtOAc/hexane=50:50) revealed a more polar product and consumption of compound 2. The mixture was poured into water (100 mL) and the product extracted into EtOAc (3×50 mL). The combined extracts were washed with brine (50 mL) followed by water (2×50 mL), and then dried over (Na2SO4) and the solvent evaporated in vacuo to furnish a residue that was subjected to silica-gel column chromatography using EtOAc/hexane (50:50) as eluent to produce 3 as a white solid (982.0 mg, 2.22 mmol, 85%).

Workup

customa more polar product and consumption of compound 2
additionThe mixture was poured into water (100 mL)
extractionthe product extracted into EtOAc (3×50 mL)
washThe combined extracts were washed with brine (50 mL)
dry with materialdried over (Na2SO4)
customthe solvent evaporated in vacuo
customto furnish a residue that

Sources & evidence

ORD record: ord-d1e2adcab6aa4593828518dfb5fb4f13
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513205B2

Reaction notes

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