|
With oxalyl dichloride; N,N-dimethyl-formamide In diethyl ether |
|
|
With thionyl chloride; N,N-dimethyl-formamide In hexane; chloroform at 60 - 65℃; for 1h; |
|
|
With thionyl chloride; N,N-dimethyl-formamide Heating; |
|
|
With oxalyl dichloride |
|
|
With thionyl chloride; N,N-dimethyl-formamide |
|
|
With oxalyl dichloride In dichloromethane at 20℃; for 2h; |
46
Add oxalyl chloride (0.20 mL, 2.30 mmol) and 3 drops of DMF to a stirring suspension of 3-phenoxy-benzoic acid (0.247 g, 1.15 mmol) in CH2Cl2 (5.0 mL). Stir the reaction mixture at room temperature for 2 h. Concentrate the mixture in vacuo, add n-hexane, re-concentrate, and re-dissolve in CH2Cl2. Add the resultant 3-phenoxy-benzoyl chloride solution to a mixture of rac- N2-methyl-N2-(l-methyl-piperidin-4-yl)-benzooxazole-2,5-diamine (0.200 g, 0.768 mmol) and pyridine (0.06 mL) in CH2Cl2 (5.0 mL). Shake the reaction mixture overnight at room temperature. Wash the mixture with saturated NaHCO3 (aqueous) (3 x 25 mL), dry the organic phase over Na2SC^, filter, and concentrate the mixture in vacuo. Subject the residue to silica gel flash column chromatography (5 x 4 g columns, eluting with 5% 2N NH3 in MeOH/CH2Cl2) to yield the desired product as a white solid (0.163 g, 46%). mass spectrum (m/e): 457.0 (M+l), 455.0 (M-I). IH NMR (400 MHz, CD3OD): δ 7.72-7.67 (m, 2H), 7.60-7.57 (m, IH), 7.51 (t, J = 7.9 Hz, IH), 7.44-7.38 (m, 2H), 7.35-7.28 (m, 2H), 7.22-7.15 (m, 2H), 7.09-7.05 (m, 2H), 4.18- 4.09 (m, IH), 3.12 (s, 3H), 3.06-3.00 (m, 2H), 2.35 (s, 3H), 2.24 (dt, / = 12.4, 2.4 Hz, 2H), 2.03- 1.92 (m, 2H), 1.87-1.80 (m, 2H). |
|
With oxalyl dichloride In dichloromethane at 20℃; |
7.1
Route 7: Step 1: Acid Chloride Formation (Int 135) 3-Phenoxy-benzoic acid (0.50 g, 0.23 mmol) was dissolved in CH2Cl2. Oxalyl chloride (0.32 g, 0.25 mmol) was added, followed by 1-2 drops of DMF. The reaction was stirred at room temperature, and then concentrated to give the desired acid chloride. |
|
With thionyl chloride for 6 - 7h; Heating / reflux; |
N-(3-PheiioxybenzoyI)-6,7-dhydroxy-l52,354-tetrahydroisoqιiinoIine (If) 3-Phenoxybenzoic acid (131 mg, 0.609 mmol) was suspended in 5 niL thionyl chloride together with a catalytical amount of DMF and refluxed for 6 hours before evaporation. The remaining residue was dissolved in 5 mL DMF and 6,7~dihydroxy- 1,2,3,4-tetrahydroisoquinoline hydrobromide (150 mg, 0.609 mmol) followed by Et3N (171 μL, 1.22 mmol) were added. The resulting mixture was stirred at room temperature for 4 hours and then diluted with 30 ml water followed by extraction with ethyl acetate (3*25mL). The combined organic phase was dried over MgSO4 and evaporated. Purification with flash chromatography (pet.ether/EtOAc 1/1 → 1/2) yielded 121 mg (54%) of N-(3-phenoxybenzoyl)-6,7-dihydroxy- 1,2,3,4-tetrahydroisoquinoline as an yellowish residue. 1H-NMR (CD3OD) rotameric mixture δ 7.47-7.31 (m, 3H), 7.20-7.05 (m, 3H), 7.05-6.89 (m, 3H), 6.61-6.50 (ma+mi)(br d, 3H) 6.32 (mi)(s, IH), 4.63 (ma)(s, 2H), 4.38 (mi)(s, 2H), 3.91-3.84 (mi)(br, 2H) 3.62-3.51 (ma)(br, 2H), 2.82-2.75 (mi)(br, 2H), 2.75-2.60 (ma)(br, 2H). TLC (pet.ether/EtOAc 1/5) R1 0.74. HRMS (ESI) calc for C22H20NO4 [M+H] 362.1392, found 362.1367; 3-Phenoxybenzoic acid (136 mg, 0.635 mmol) was suspended in 5 mL thionyl chloride together with a catalytical amount of DMF and refluxed for 7 hours before evaporation. The remaining residue was dissolved in 5 mL DMF and 5,8-dichloro-6,7- dihydroxy-l,2,3,4-tetrahydroisoquinoline hydrobromide (200 mg, 0.635 mmol) followed by Et3N (178 μL, 1.27 mmol) were added. The resulting mixture was stirred at room temperature for 8 hours and then diluted with 30 ml water followed by extraction with ethyl acetate (3*25mL). The combined organic phase was dried over MgSO4 and evaporated. Purification with flash chromatography (pet.ether/EtOAc 1/1 → 1/2) yielded 108 mg (40%) of N-(3-ρhenoxybenzoyl)-5,8-dichloro-6,7-dihydroxy-l,2,3,4- tetrahydroisoquinoline as a pale residue. 1H-NMR (CDCl3) rotameric mixture δ 7.46-7.31 (m, 3H), 7.20-7.01 (m, 6H), 4.76 (ma)(br s, 2H), 4.51 (mi)(br s, 2H), 4.01-3.90 (mi)(br, 2H) 3.68-3.57 (ma)(br, 2H), 2.92-2.81 (mi)(br, 2H), 2.81-2.70 (ma)(br, 2H). TLC (pet.ether/EtOAc 1/5) Rf 0.73. HRMS (ESI) calc for C22Hi7NO4NaCl2 [M+Na] 452.0432, found 452.0370. |
|
With thionyl chloride In chloroform for 0.5h; Reflux; |
General procedure: A mixture of 4a-g (1.85 mmol), thionyl chloride (28 mmol) in chloroform (5 mL) was heated at reflux for 30 minutes. The resulting solution was evaporated under reduced pressure to remove excess thionyl chloride. The residual liquid was added in one portion to a solution of the substituted aniline 5a-u (2.03 mmol), triethylamine (2.31 mmol) and dichloromethane (5 mL) at 0 °C. The reaction mixture was stirred at room temperature for 2-8 h. It was then treated with 2M HCl, saturated sodium bicarbonate solution, brine, and dried over Na2SO4. The solvent was removed and the resulting solid was purified by flash column chromatography or recrystalization from ethanol to afford the title compounds 6a-v. |
|
With thionyl chloride at 60 - 80℃; |
|
|
With oxalyl dichloride In hexane; N,N-dimethyl-formamide at 20℃; for 1h; |
|
|
With thionyl chloride In N,N-dimethyl-formamide at 80℃; for 4h; |
|
|
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane for 4h; Reflux; |
|
|
With phosphorus pentachloride |
|
|
With thionyl chloride In dichloromethane for 4h; Reflux; Inert atmosphere; Schlenk technique; |
|
|
With thionyl chloride for 2h; Reflux; |
|
|
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0℃; for 1h; Inert atmosphere; |
|
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1.5h; Inert atmosphere; |
|
|
With thionyl chloride; N,N-dimethyl-formamide at 79℃; for 3h; |
|
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; |
1 Step 1: Acid Chloride Formation (Int 135)
3 -Phenoxy -benzoic acid (0.50 g, 0.23 mmol) was dissolved in CH2CI2. Oxalyl chloride (0.32 g, 0.25 mmol) was added, followed by 1-2 drops of DMF. The reaction was stirred at room temperature, and then concentrated to give the desired acid chloride. |
|
With thionyl chloride Reflux; |
5.1.18. General procedure 2 for preparation of 64-81, 83-91
General procedure: To a solution of organic acids (1.1 eq) in SOCl2, the reaction wasstirred at reflux, then finished, SOCl2 was removed and 5 mL THFwas added and dropwise to compound 26 (1.0 eq). Mixture wasstirred at r.t overnight. Then solvent was removed, H2O and ethylacetate was added, organic layer was dried by anhydrous Na2SO4and concentrated. Next, to a solution of compounds gained above inethyl acetate, HCl gas was added for 0.5 h, filtered the solid to affordproducts. |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
HazMat Fee +
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
