Reference of 96-30-0, A common heterocyclic compound, 96-30-0, name is 2-Chloro-N-methylacetamide, molecular formula is C3H6ClNO, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
A suspension of Intermediate 7 (500 mg, 1.48 mmol), K2C03 (204 mg, 1.48 mmol) and potassium thioacetate (590 mg, 5.16 mmol) in DMF (5.5 mL) was heated at 140C under microwave irradiation for 3 h. After cooling, the mixture was dissolved in water (20 mL), neutralized to pH 6 with 1M HCl and extracted with EtOAc (3 x 50 mL). The organic layer was washed with saturated brine (3 x 30 mL), dried (MgS04) and concentrated in vacuo. Purification by column chromatography on silica, eluting with 5% EtOAc in DCM, gave a yellow solid (127 mg, 26%). LCMS (ES+) 337 (M+H)+. A suspension of this solid (114 mg, 0.339 mmol), K2C03 (46.8 mg, 0.339 mmol) and 2- chloro-N-methylacetamide (87 mg, 0.809 mmol) in DMF (3 mL) was heated at 120C under microwave irradiation for 1 h. After cooling, the mixture was dissolved in a 1 : 1 mixture of EtOAc and Et20 (150 mL) and washed with saturated brine (3 x 30 mL). The organic layer was dried (MgS04) and concentrated in vacuo. Purification by column chromatography on silica, eluting with 40% EtOAc in DCM, gave a white solid (119 mg, 86%). LCMS (ES+) 408 (M+H)+. This solid (119 mg, 0.292 mmol) was dissolved in DCM (7.6 mL) and TFA (1.33 mL) was added. The reaction mixture was stirred at r.t. for 1.5 h and concentrated in vacuo. The residue obtained was basified with 0.8M aqueous NaOH (8 mL) and extracted with EtOAc (3 x 30 mL). The combined organic layers were dried (MgS04) and concentrated in vacuo to give a colourless glass (117 mg, 100%). LCMS (ES+) 308 (M+H)+. A solution of this material (117 mg, 0.292 mmol), 2,4-dichloro-5-cyanopyrimidine (76.2 mg, 0.438 mmol) and DIPEA (0.20 mL, 1.168 mmol) in THF (2 mL) was stirred at r.t. for 4 h. The mixture was dissolved in EtOAc (150 mL) and washed with saturated brine (3 x 30 mL). The organic layer was dried (MgS04) and concentrated in vacuo. Purification by column chromatography on silica, eluting with DCM/MeOH NH3 solution in MeOH (98: 1 :1), gave a pale brown foam (105 mg, 81%). LCMS (ES+) 445, 447 (M+H)+ (mixture of regioisomers). A solution of this material (105 mg, 0.236 mmol) in a mixture of 7M NH3 solution in MeOH (2 mL) and NH4OH (1 mL) was heated at 120C under microwave irradiation for 1 h. After cooling, the mixture was dissolved in saturated brine (40 mL) and extracted with EtOAc (3 x 100 mL). The organic layer was dried (MgS04) and concentrated in vacuo. Purification by preparative HPLC afforded the title compound (13.2 mg, 13%) as an off-white solid, delta? (DMSO-d6) 8.31 (1H, s), 8.25 (1H, s), 8.15 (1H, d, J5.33 Hz), 7.87-7.81 (2H, m), 7.40 (1H, t, J9.13 Hz), 7.15 (1H, br s), 6.97 (1H, br s), 5.55-5.46 (1H, m), 4.10 (1H, d, J 15.2 Hz), 4.04 (1H, d, J 15.2 Hz), 2.65 (3H, d, J4.59 Hz), 2.58 (3H, s), 1.61 (3H, d, J 6.82 Hz). LCMS (ES+) 426 (M+H)+, T 3.37 minutes {Method 1).
The synthetic route of 96-30-0 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; UCB PHARMA S.A.; RAPHY, Gilles; BUeRLI, Roland; HAUGHAN, Alan, Findlay; WO2011/58113; (2011); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics