Hydrochloric Acid → 4-(2-Fluoro-5-methylanilino)-2-(4-hydroxyanilino)pyrimidine

HRID 347758Notes

Reaction equation

[F:1][C:2]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:3]=1[NH:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7](Cl)[N:6]=1.[OH:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1.Cl.C(OCC)C>CN1C(=O)CCC1>[F:1][C:2]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:3]=1[NH:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:22][C:21]2[CH:23]=[CH:24][C:18]([OH:17])=[CH:19][CH:20]=2)[N:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

4-(2-Fluoro-5-methylanilino)-2-chloropyrimidine (Reference Example A-10, 1.00 g, 4.2 mmol) was dissolved in NMP (5 ml) and 4-hydroxyaniline (0.41 g, 3.7 mmol) and 1M HCl in diethyl ether (4.22 ml, 4.2 mmol) was added. The reaction mixture was heated at 100° C. for 15 hours, and then allowed to cool to ambient temperature. The mixture was evaporated under high vacuum to give the title product as a brown oil. The residue was purified by chromatography on a Mega Bond Elute column (10 g) eluting with DCM (4×25 ml), 2% NH3/MeOH in DCM (3×25 ml), 4% NH3/MeOH in DCM (3×25 ml), 6% NH3/MeOH in DCM (10×25 ml to give the title product as a white solid (0.80 g, 61%). NMR (300 MHz): 2.2 (s, 3H), 6.2 (d, 1H), 6.6 (d, 2H), 6.9 (m, 1H), 7.1 (m, 1H), 7.4 (d, 2H), 7.8 (d, 1H), 7.9 (d, 1H), 8.7 (s, 1H), 8.8 (s, 1H), 8.9 (s, 1H); m/z: (ES+) 311.0 (MH+).

Workup

temperatureto cool to ambient temperature
customThe mixture was evaporated under high vacuum

Sources & evidence

ORD record: ord-d67e327154ec4bd392556db35e9c6cae
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07176212B2

Reaction notes

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