Triethylamine → 6-chloro-N-(4-methoxybenzyl)-2-methylpyrimidin-4-amine

HRID 1621640Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([CH3:9])[N:3]=1.[CH3:10][O:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16][NH2:17])=[CH:14][CH:13]=1.C(N(CC)CC)C>CN(C=O)C>[Cl:8][C:6]1[N:5]=[C:4]([CH3:9])[N:3]=[C:2]([NH:17][CH2:16][C:15]2[CH:18]=[CH:19][C:12]([O:11][CH3:10])=[CH:13][CH:14]=2)[CH:7]=1

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of 4,6-dichloro-2-methylpyrimidine (Aldrich) (1.45 g, 8.90 mmol), 4-methoxybenzylamine (Alfa Aesar) (1.278 mL, 9.78 mmol), and triethylamine (1.488 mL, 10.67 mmol) in DMF (10.0 mL) was stirred at 25° C. for 18 h. The resulting mixture was partitioned between EtOAc (300 mL) and half-saturated aqueous NaHCO3 (80 mL). The organic layer was separated, sequentially washed with water (2×80 mL) and brine (80 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (ISCO, 120 g, 0 to 100% EtOAc/Hexanes) furnished 6-chloro-N-(4-methoxybenzyl)-2-methylpyrimidin-4-amine (2.30 g, 8.72 mmol, 98% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 7.23 (d, J=8.41 Hz, 2H); 6.89 (d, J=8.61 Hz, 2H); 6.18 (s, 1H); 4.42 (br. s., 2H); 3.81 (s, 3H); 2.50 (s, 3H). m/z (ESI, +ve ion) 264.1 (M+H)+.

Workup

customThe resulting mixture was partitioned between EtOAc (300 mL) and half-saturated aqueous NaHCO3 (80 mL)
customThe organic layer was separated
washsequentially washed with water (2×80 mL) and brine (80 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customChromatographic purification of the residue (ISCO, 120 g, 0 to 100% EtOAc/Hexanes)

Sources & evidence

ORD record: ord-fb54d250412a4fb0a7165fb5fa034e51
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772480B2

Reaction notes

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