2-Chloromethyl 2-(trimethylsilyl)ethyl ether → HCID 66773299, compound

Participants

Reaction Steps

A 250 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 3.3 g of 3-bromo-5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile in 85 ml of DMF, 10.6 ml of N,N-diisopropylethylamine and 3.2 ml of 2-(trimethylsilyl)ethoxymethyl chloride. After 5 h at RT, the mixture is poured into 8 volumes of ice-water. The aqueous phase is extracted with 3 times 200 ml of AcOEt, and the organic extracts are combined, washed with saturated NaCl solution, dried over MgSO4 and concentrated under RP. Purification is carried out by flash chromatography on silica gel (40-63 μm), eluting with a mixture of DCM and methanol (99.5/0.5 by vol.), to give on one hand 2.1 g of 3-bromo-5-(2,6-difluorophenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile in the form of a white solid. MS (E/I): m/z=515 (M+); 1H NMR: −0.12 (s, 9H); 0.87 (t, J=8.0 Hz, 2H); 3.65 (t, J=8.0 Hz, 2H); 6.17 (s, 2H); 7.40 (t, J=8.0 Hz, 2H); 7.77 (m, 1H); 8.41 (broad s, 1H); 8.47 (dd, J=1.5 and 8.5 Hz, 1H); 8.77 (d, J=8.5 Hz, 1H). And, on the other hand, 1.2 g of 3-bromo-5-(2,6-difluorophenyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile (white solid). MS (E/I): m/z=515 (M+); 1H NMR: −0.05 (s, 9H); 0.90 (t, J=8.0 Hz, 2H); 3.73 (t, J=8.0 Hz, 2H); 5.92 (s, 2H); 7.38 (t, J=8.0 Hz, 2H); 7.76 (m, 1H); 8.24 (broad s, 1H); 8.34 (dd, J=1.5 and 8.5 Hz, 1H); 8.69 (d, J=8.5 Hz, 1H).

Provenance & Evidence