Potassium Acetate → 4-(5-chloro-2-fluoropyridin-3-yl)-N-(2-methoxyethyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1812082Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][CH2:10][CH2:11][O:12][CH3:13])[N:3]=1.[Cl:14][C:15]1[CH:16]=[C:17](B(O)O)[C:18]([F:21])=[N:19][CH:20]=1.C([O-])(=O)C.[K+]>O1CCOCC1.Cl[Pd]Cl>[Cl:14][C:15]1[CH:16]=[C:17]([C:2]2[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][CH2:10][CH2:11][O:12][CH3:13])[N:3]=2)[C:18]([F:21])=[N:19][CH:20]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-chloro-N-(2-methoxyethyl)-6-methyl-1,3,5-triazin-2-amine (300 mg, 1.480 mmol), 5-chloro-2-fluoropyridin-3-ylboronic acid (320 mg, 1.825 mmol), potassium acetate (298 mg, 3.04 mmol), and Am-phos PdCl2 (47 mg, 0.066 mmol) in dioxane (10 mL) was heated at 100° C. under nitrogen. After 6 h, the mixture was cooled to rt and partitioned between water (10 mL) and EtOAc (20 mL). The organic layer was dried over Na2SO4 and concentrated. The oil was purified on silica using EtOAc in hexane (10-80%) to give the product as a yellow solid (130 mg). LCMS (ES, pos.): calcd for C12H13ClFN5O: 297.1. found: 298.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.55 (ddd, J=16.24, 7.92, 2.64 Hz, 1H); 8.27 (br. s., 1H); 5.91 (br. s., 1H); 3.72 (quin, J=5.62 Hz, 2H); 3.59 (t, J=5.09 Hz, 2H); 3.40 (2s, 3H); 2.51 (2s, 3H).

Workup

temperaturethe mixture was cooled to rt
custompartitioned between water (10 mL) and EtOAc (20 mL)
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated
customThe oil was purified on silica

Sources & evidence

ORD record: ord-48a3a10812bb4b099f3f1895966dc90a
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362241B2

Reaction notes

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