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

HRID 1621670Notes

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-cb58f957d4f74aa8bf884e2a73d9ad3c
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772480B2

Reaction notes

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