反应详情

A mixture of methyl 2,6-diamino-5-chloronicotinate (EXAMPLE 1, METHOD B, Step 1, 2.0 g, 9.92 mmol) and chloroacetaldehyde (1.2 mL, 10.91 mmol) in methanol (100 mL) was refluxed for 135 min. A further chloroacetaldehyde (1.2 mL, 10.91 mmol) was added and refluxing continued over 21 hours. The solvent was evaporated and the resulting solid co-evaporated with methanol (75 mL×2) prior to drying under vacuum, giving 2.62 g of crude material. The residue was chromatographed on a column of silica gel eluting with dichloromethane/methanol/25% aqueous ammonia (96.5:3.5:0.5 to 93:7:1) to give 1.52 g (68%) of the title compound as an off white powder.

1. temperaturewas refluxed for 135 min
2. temperaturerefluxing
3. customThe solvent was evaporated
4. dry with materialthe resulting solid co-evaporated with methanol (75 mL×2) prior to drying under vacuum
5. customgiving 2.62 g of crude material
6. customThe residue was chromatographed on a column of silica gel eluting with dichloromethane/methanol/25% aqueous ammonia (96.5:3.5:0.5 to 93:7:1)