4-CHLOROTHIENO[2,3-D]PYRIMIDINE

Slightly Yellowish Crystalline Solid

DMF (1.53 ml, 19.7 mmol) in dichloromethane (50 ml) was cooled to 0° C. and oxalyl chloride (2.5 ml, 29.6 mmol) was added slowly forming a white gel. Thieno[2, 3-d]pyrimidin-4(3H)-one (1.5 g, 9.86 mmol) was added and the reaction mixture was refluxed for 3 hours. The mixture was cooled down to room temperature and poured into water. The mixture was extracted with dichloromethane, dried over sodium sulfate and concentrated in vacuo. The crude residue was purified by silica gel chromatography (EtOAc/hexane 15:1) to yield the title compound as a white solid (1.61 g, 96percent).Example 307 General procedure: The different thieno[2, 3-d]pyrimidin-4-one (6a-d or f-i) (1 eq.) and phosphoryl chloride (2.9 mL/mmoleq.) were refluxed for 8 h. The reaction mixture was then cooled in an ice-bath and carefully neutralised by the addition of aqueous saturated NaHCO3 solution. The resulting mixture was extracted with ethylacetate (15 mL/mmol eq.), the organic layer was separated, dried over MgSO4 and concentrated. The crude residue was purified by flash column chromatography eluting with n-hexane-EtOAc 100:0 v/vincreasing to n-hexane-EtOAc 85:15 v/v unless otherwise stated.4-Hydroxythieno[2, 3-d]pyrimidine (1.0g, 6.6mmol) was suspended in 3.9mL acetonitrile. Triethylamine (1.83mL, 13.12mmol)was added dropwise to the stirred reaction mixture. Subsequently, phosphorus oxychloride (1.26mL, 13.48mmol) was addeddropwise. The reaction mixture stirred at 100°C for one hour and then cooled to room temperature. The reaction was quenchedby addition of ice water. The product precipitated from the solution and was isolated by filtration. Yield 785mg, 70percent, beigesolid.Thieno[2, 3-d]pyrimidin-4-ol (10.0 g, 66 mmol) was added to a 250 mL round bottom flaskWith 100 mL of 1, 4-dioxane, the mixture was stirred at 0°C.Phosphorus oxychloride (20 mL, 212 mmol) was gradually added dropwise to the reaction system.The mixture was heated at 90 °C with stirring for 3 h.Cool to room temperature, quench the reaction with aqueous sodium hydroxide, and extract with dichloromethane.Rotary evaporator removes solvent.Purification by column chromatography. A white solid (9.1 g, 60percent) was obtained.Thieno[2, 3-d]pyrimidin-4(3H)-one(1.2 g, 7.9 mmol) was diluted in 1, 2-dichloroethane (1OmL). Phosphorous oxychloride (1.4 mL, 15.7 mmol) was added. The reaction was stirred at 90°C for 16 hours. An additional equivalent of phosphorous oxychloride (0.7 mL, 7.9 mmol) was added and the solution continued stirring for 4 hours. The solution was cooled, concentrated, and neutralized with saturated NaHCOA solution of intermediate b (5.102 g, 0.033 mol) was added to toluene (100 mL) and its phosphorus oxychloride (30 ml) 90 °C for 2 hours. The reaction solution was cooled and then added dropwise to ice water, The filter cake was dried to give a yellow powder of 2.432 g in a yield of 43.4percent.Step 2: (0356) Phosphorus oxychloride (10 ml) was added into compound 13-b (500 mg, 3.23 mmol) followed by stirring at reflux overnight. The reaction mixture was cooled to room temperature, poured into a vigorously stirred ice-water mixture and stirring was continued for 30 minutes. The mixture was extracted with dichloromethane (50 ml×3). The combined organic phase was washed with brine, dried over anhydrous sodium sulfate, and concentrated to give 13-c as a yellow solid (600 mg, yield: 100percent). ESI-MS (m/z): 170.9 [M+H]2nd step: 250 ml single-port bottle adding CP0763A 45g, phosphorus oxychloride 75 ml and N, N - dimethyl aniline 7.5 ml, heating reflux 2 hours for inspection, raw material of reaction. After the steaming and remove most of the phosphorus oxychloride, adding ice water quenching. Then the pH is adjusted with ammonia water 6 - 7, filtering, the filter cake is washed for three times. Solid dissolves clear EA adding activated carbon to decolorize. Drying reciprocation product job (CP0763 B) 34g. Yield: 68percent;Example 307

Molecular Weight:170.62
XLogP3:2.1
Hydrogen Bond Acceptor Count:3
Exact Mass:169.9705470
Monoisotopic Mass:169.9705470
Topological Polar Surface Area:54
Heavy Atom Count:10
Complexity:133
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes