4-Chloro-6-methyl-1,3,5-triazin-2-amine → 4-(2-Fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621377Notes

Reaction equation

O1CCOCC1.Cl[C:8]1[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH2:15])[N:9]=1.[F:16][C:17]1[C:22](B(O)O)=[CH:21][CH:20]=[CH:19][N:18]=1.C([O-])(=O)C.[K+]>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:16][C:17]1[C:22]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH2:15])[N:9]=2)=[CH:21][CH:20]=[CH:19][N:18]=1

Participants

Conditions

Temperature: 100 °C

Procedure

1,4-Dioxane (6.00 mL, 2927 μmol) was added to a mixture of 4-chloro-6-methyl-1,3,5-triazin-2-amine (423.1 mg, 2927 μmol), 2-fluoropyridin-3-ylboronic acid (619 mg, 4390 μmol), bis(di-tert-butyl (4-dimethylaminophenyl)phosphine)dichloropalladium(II) (91.0 mg, 146 μmol) and potassium acetate (862 mg, 8780 μmol) and the mixture was heated at 100° C. overnight. After cooling, the mixture was passed through a short plug of Celite® (diatomaceous earth). The filter cake was washed with EtOAc (3×15 mL). The combined organic phases were concentrated to give a crude residue. Flash column chromatographic purification (short column, SiO2, pure DCM to 3% MeOH in DCM) provided the title compound which was washed with MeOH to give 4-(2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (454 mg, 76%) as a pale brown powder. LCMS (API-ES) m/z 206 (M+H)+; 1H NMR (400 MHz, d6-DMSO) δ 8.48 (ddd, J=9.91, 7.65, 2.01 Hz, 1H) 8.39 (d, J=5.02 Hz, 1H) 7.65 (br. s., 2H) 7.51 (ddd, J=7.15, 5.14, 1.76 Hz, 1H) 2.37 (s, 3H).

Workup

temperatureAfter cooling
washThe filter cake was washed with EtOAc (3×15 mL)
concentrationThe combined organic phases were concentrated
customto give a crude residue
customFlash column chromatographic purification (short column, SiO2, pure DCM to 3% MeOH in DCM)

Sources & evidence

ORD record: ord-501c09e0117f4543ae01e5363a514495
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772480B2

Reaction notes

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