Sodium hydride → 2-Methyl-8-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-quinoxaline

HRID 2055943Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[N:5]=[CH:4][N:3]=1.[CH3:18][C:19]1[CH:20]=[N:21][C:22]2[CH:23]=[CH:24][CH:25]=[C:26]([OH:29])[C:27]=2[N:28]=1.[H-].[Na+]>CN(C=O)C>[CH3:18][C:19]1[CH:20]=[N:21][C:22]2[C:27](=[C:26]([O:29][C:2]3[CH:7]=[C:6]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=4)[N:5]=[CH:4][N:3]=3)[CH:25]=[CH:24][CH:23]=2)[N:28]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a mixture of 4-chloro-6-(4-trifluoromethyl-phenyl)-pyrimidine, (Example 2(a), Method A), (0.20 g, 0.77 mmol) and 3-methyl-quinoxalin-5-ol (0.14 g, 0.85 mmol, prepared according to J. Med. Chem. 1988, 41, 4062-4079.) in DMF (3 mL) was added sodium hydride (0.040 g, 1.0 mmol, 60% dispersion in mineral oil, Aldrich). The reaction was heated at 60° C. for 24 h, allowed to cool to room temperature and partitioned between EtOAc and H2O. The aqueous layer was extracted with EtOAc (4 x). The combined organic layers were dried over MgSO4, filtered and the solvent was removed in vacuum. The residue was purified by flash chromatography (0→75% EtOAc/hexanes) to give the title compound as an ivory powder. Mp: 139-141° C., MS (ESI, pos. ion) m/z: 383 (M+1).

Workup

temperatureto cool to room temperature
custompartitioned between EtOAc and H2O
extractionThe aqueous layer was extracted with EtOAc (4 x)
dry with materialThe combined organic layers were dried over MgSO4
filtrationfiltered
customthe solvent was removed in vacuum
customThe residue was purified by flash chromatography (0→75% EtOAc/hexanes)

Sources & evidence

ORD record: ord-993104766a4f44639d86bfecbfdfff1b
Source dataset: uspto-grants-2008_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07332511B2

Reaction notes

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