* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
The intermediate 1 was dissolved in 20percent aqueous ammonia, and the reaction was stirred at room temperature for 20 hours. After the reaction was completed, 50 mL of ethyl acetate was added and extracted three times.The organic layer was combined, and the solvent was evaporated to dryness to give Intermediate 2,White solid, 2.5 g, yield 76percent.
59%
With ammonia In water at 20℃; for 64 h;
PREPARATION 17; Preparation of (S)-3-phenylpropane-l,2-diamine; A. A mixture of L-phenylalanine methyl ester hydrochloride (6.50 g, 30.1 mmol) and ammonium hydroxide solution (28percent in water, 15 mL) in water (60 mL) was stirred at ambient temperature for 64 h. The aqueous layer was extracted with dichloromethane (6 x 100 mL), and the combined organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford (5)-2-amino-3-phenylpropanamide as a colorless solid in 59percent yield (2.92 g): 1H NMR (300 MHz, DMSO-4) δ 7.38-7.21
19.5 g
Stage #1: With sodium hydrogencarbonate In chloroform Stage #2: With ammonium hydroxide In toluene at 20℃; for 24 h;
To a solution of L-Phenylalanine methyl ester hydrochloride (26.1 g, 121 mmol, 1 eq) in chloroform (200 ml) was added saturated NaHC03 solution until pH paper indicated the solution to be basic. The free amine was extracted with chloroform (2 x 200 ml), dried over MgS04 and evaporated under reduced pressure. The resulting L-Phenylalanine methyl ester was dissolved in toluene (300 ml) and to this solution was added saturated ammonium hydroxide solution (150 ml). The reaction was stirred at room temperature for 24 hours before being evaporated to dryness under reduced pressure. The crude product did not require further purification (19.5 g, 1 19 mmol, 98 percent). 1H NMR (400 MHz, DMSO): δ = 1 .90 (brs, 2H, NH2), 2.59 (dd, J = 13.4 Hz, 8.3 Hz, 1 H), 2.92 (dd, J = 13.4 Hz, J = 5.1 Hz, 1 H), 3.34 (dd, J = 8.3 Hz, 5.1 Hz, 1 H), 6.96 (brs, 1 H), 7.16-7.30 (m, 5H), 7.32 (brs, 1 H); 13C NMR (100.6 MHz, CDCI3): δ = 42.0, 57.1 , 126.9, 128.9, 130.2, 139.8, 177.6.
Reference：
[1] Helvetica Chimica Acta, 2004, vol. 87, # 5, p. 1077 - 1089
[2] Organic and Biomolecular Chemistry, 2012, vol. 10, # 30, p. 6074 - 6086
[3] Chemistry - An Asian Journal, 2011, vol. 6, # 6, p. 1321 - 1324
[4] Bulletin de la Societe Chimique de France, 1989, # 5, p. 673 - 676
[5] Patent: CN108610292, 2018, A, . Location in patent: Paragraph 0041; 0051; 0052
[6] Chemistry - A European Journal, 2006, vol. 12, # 26, p. 6910 - 6929
[7] Patent: WO2008/127349, 2008, A2, . Location in patent: Page/Page column 104
[8] Bulletin de la Societe Chimique de France, 1991, # 3, p. 423 - 429
[9] European Journal of Medicinal Chemistry, 1985, vol. 20, # 6, p. 509 - 512
[10] European Journal of Medicinal Chemistry, 1986, vol. 21, # 4, p. 333 - 338
[11] Journal of the American Chemical Society, 2005, vol. 127, # 30, p. 10504 - 10505
[12] Tetrahedron Asymmetry, 2008, vol. 19, # 24, p. 2804 - 2815
[13] Chemistry - A European Journal, 2008, vol. 14, # 35, p. 10888 - 10891
[14] Patent: WO2014/68341, 2014, A2, . Location in patent: Page/Page column 41
5
[ 2577-90-4 ]
[ 5241-58-7 ]
Yield
Reaction Conditions
Operation in experiment
48 g
With ammonium hydroxide In methanol; water at 20℃; for 72 h; Inert atmosphere
Into a 1000 mE 24/40 joint single neck round bottomed flask equipped with a stir bar under nitrogen sparge was added a solution comprising 45.7 grams of (5)-Phenylalanine methyl ester (0.255 mol) in 200 mE MeOH. Aqueous NH4OH (28-30percent, 200 mE) was then added dropwise over approximately 20 minutes. The reaction was stirred 72 h under N2 atmosphere, and then concentrated under vacuum (.-5 -10 mm Hg) on a rotovap (l3uchi Rotovapor R-124, I3UCHI Eabortecimik AG, Switzerland). The residue was dissolved in water (250 mE) at RT and extracted with CH2C12 (5x500 mE) using a separatory thnnd. The organic layers were combined into a 4 E Erlenmeyer flask, dried (anhydrous Na2504), filtered to remove drying agent and concentrated via rotovap under vacuum (5-10mm Hg) to provide a white solid; 48 grams.
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1985, p. 461 - 470
[2] Synthesis, 1976, p. 685 - 687
[3] Journal of the Chemical Society. Perkin transactions 1, 1966, vol. 5, p. 555 - 566
[4] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1985, p. 697 - 702
[5] Journal of the Chemical Society, Faraday Transactions 1: Physical Chemistry in Condensed Phases, 1985, vol. 81, p. 2207 - 2214
[6] Journal of Organic Chemistry, 2000, vol. 65, # 24, p. 8229 - 8238
[7] Russian Journal of Bioorganic Chemistry, 2005, vol. 31, # 2, p. 119 - 127
[8] Chemical Communications, 2016, vol. 52, # 89, p. 13147 - 13150
7
[ 88463-18-7 ]
[ 5241-58-7 ]
Reference：
[1] Chemical Physics Letters, 2001, vol. 341, # 1-2, p. 99 - 106
[2] Synlett, 2002, # 11, p. 1845 - 1849
[3] Synthesis, 2003, # 4, p. 603 - 622
[4] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 4, p. 1694 - 1702
[5] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7355 - 7358
[6] RSC Advances, 2013, vol. 3, # 37, p. 16810 - 16816
8
[ 65864-22-4 ]
[ 5241-58-7 ]
Reference：
[1] Patent: US2006/223855, 2006, A1, . Location in patent: Page/Page column 139
[2] Biochemical Journal, 2013, vol. 451, # 2, p. 329 - 342
[3] Chemical Communications, 2016, vol. 52, # 89, p. 13147 - 13150
9
[ 55379-75-4 ]
[ 5241-58-7 ]
Reference：
[1] Patent: US4918196, 1990, A,
[2] Patent: US4918196, 1990, A,
10
[ 63-91-2 ]
[ 543-27-1 ]
[ 5241-58-7 ]
Reference：
[1] Patent: US5736520, 1998, A,
11
[ 63-91-2 ]
[ 5241-58-7 ]
Reference：
[1] Journal of the Chemical Society, Faraday Transactions 1: Physical Chemistry in Condensed Phases, 1985, vol. 81, p. 2207 - 2214
[2] Bulletin de la Societe Chimique de France, 1989, # 5, p. 673 - 676
[3] European Journal of Medicinal Chemistry, 1986, vol. 21, # 4, p. 333 - 338
[4] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1985, p. 461 - 470
[5] European Journal of Medicinal Chemistry, 1985, vol. 20, # 6, p. 509 - 512
[6] Bulletin de la Societe Chimique de France, 1991, # 3, p. 423 - 429
[7] Phosphorus, Sulfur and Silicon and the Related Elements, 2015, vol. 190, # 8, p. 1285 - 1293
[8] Patent: US2017/57911, 2017, A1,
[9] Patent: CN108610292, 2018, A,
12
[ 63-91-2 ]
[ 6638-79-5 ]
[ 543-27-1 ]
[ 5241-58-7 ]
Reference：
[1] Patent: EP410411, 1991, A2,
13
[ 73148-70-6 ]
[ 5241-58-7 ]
Reference：
[1] Chemical Communications, 2016, vol. 52, # 89, p. 13147 - 13150
14
[ 13734-34-4 ]
[ 5241-58-7 ]
Reference：
[1] Journal of the Chemical Society - Perkin Transactions 1, 1996, # 20, p. 2479 - 2485
[2] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 4, p. 1694 - 1702
[3] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7355 - 7358
[4] Journal of Medicinal Chemistry, 2017, vol. 60, # 5, p. 2119 - 2134
15
[ 47091-50-9 ]
[ 70-47-3 ]
[ 5241-58-7 ]
Reference：
[1] Chemistry - A European Journal, 2000, vol. 6, # 21, p. 3906 - 3913
16
[ 1161-13-3 ]
[ 5241-58-7 ]
Reference：
[1] Journal of the Chemical Society, Faraday Transactions 1: Physical Chemistry in Condensed Phases, 1985, vol. 81, p. 2207 - 2214
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1985, p. 461 - 470
[3] Journal of the Chemical Society. Perkin transactions 1, 1966, vol. 5, p. 555 - 566
17
[ 3081-24-1 ]
[ 5241-58-7 ]
Reference：
[1] Journal of the American Chemical Society, 1951, vol. 73, p. 1131
[2] Journal of the Chemical Society, 1964, p. 3973 - 3981
18
[ 2578-84-9 ]
[ 5241-58-7 ]
Reference：
[1] Russian Journal of Bioorganic Chemistry, 2005, vol. 31, # 2, p. 119 - 127
19
[ 112667-29-5 ]
[ 5241-58-7 ]
Reference：
[1] Journal of Medicinal Chemistry, 2013, vol. 56, # 7, p. 2841 - 2849
Reference：
[1] Journal of the Chemical Society, Chemical Communications, 1988, # 5, p. 382 - 384
[2] Journal of Medicinal Chemistry, 2013, vol. 56, # 7, p. 2841 - 2849
Reference：
[1] Bulletin de la Societe Chimique de France, 1993, vol. 130, p. 513 - 520
[2] Bulletin de la Societe Chimique de France, 1993, vol. 130, p. 513 - 520
26
[ 155385-80-1 ]
[ 5241-58-7 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1993, vol. 130, p. 513 - 520
27
[ 17193-31-6 ]
[ 5241-58-7 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1991, # 3, p. 423 - 429
28
[ 21947-21-7 ]
[ 5241-58-7 ]
Reference：
[1] Chemical Communications, 2016, vol. 52, # 89, p. 13147 - 13150
29
[ 513-49-5 ]
[ 5241-58-7 ]
Reference：
[1] Journal of the American Chemical Society, 2008, vol. 130, # 2, p. 522 - 534
30
[ 13250-12-9 ]
[ 5241-58-7 ]
Reference：
[1] Journal of the American Chemical Society, 2008, vol. 130, # 2, p. 522 - 534
31
[ 513-49-5 ]
[ 5241-58-7 ]
Reference：
[1] Journal of the American Chemical Society, 2008, vol. 130, # 2, p. 522 - 534
32
[ 13250-12-9 ]
[ 5241-58-7 ]
Reference：
[1] Journal of the American Chemical Society, 2008, vol. 130, # 2, p. 522 - 534
33
[ 73148-50-2 ]
[ 5241-58-7 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1987, vol. 35, # 1, p. 60 - 71
34
[ 24730-33-4 ]
[ 5241-58-7 ]
Reference：
[1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1982, vol. 21, # 8, p. 740 - 743
35
[ 17193-31-6 ]
[ 63-91-2 ]
[ 5241-58-7 ]
[ 673-06-3 ]
[ 5241-58-7 ]
Reference：
[1] Journal of Organic Chemistry, 2002, vol. 67, # 18, p. 6542 - 6545
[2] Journal of Organic Chemistry, 2002, vol. 67, # 18, p. 6542 - 6545
36
[ 86060-92-6 ]
[ 5241-58-7 ]
Reference：
[1] Collection of Czechoslovak Chemical Communications, 1988, vol. 53, # 11B, p. 2791 - 2800
Stage #1: methyl (2S)-2-amino-3-phenylpropanoate hydrochloride With triethylamine In methanol; diethyl ether at -10℃; for 2h;
Stage #2: With ammonia In methanol for 48h;
79%
With ammonia In water at 20℃; Inert atmosphere;
79%
With ammonium hydroxide at 20℃; for 10h;
78%
With ammonium hydroxide for 96h; Ambient temperature;
76%
With ammonium hydroxide at 20℃;
Intermediate 2:
The intermediate 1 was dissolved in 20% aqueous ammonia, and the reaction was stirred at room temperature for 20 hours. After the reaction was completed, 50 mL of ethyl acetate was added and extracted three times.The organic layer was combined, and the solvent was evaporated to dryness to give Intermediate 2,White solid, 2.5 g, yield 76%.
74%
With ammonium hydroxide In toluene
71%
With ammonium hydroxide at 20℃; for 24h; Cooling with ice;
59%
With ammonia In water at 20℃; for 64h;
17.A
PREPARATION 17; Preparation of (S)-3-phenylpropane-l,2-diamine; A. A mixture of L-phenylalanine methyl ester hydrochloride (6.50 g, 30.1 mmol) and ammonium hydroxide solution (28% in water, 15 mL) in water (60 mL) was stirred at ambient temperature for 64 h. The aqueous layer was extracted with dichloromethane (6 x 100 mL), and the combined organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford (5)-2-amino-3-phenylpropanamide as a colorless solid in 59% yield (2.92 g): 1H NMR (300 MHz, DMSO-4) δ 7.38-7.21
With ammonia In methanol Ambient temperature;
With ammonia In methanol at 0℃; for 144h;
With ammonia In methanol at 0℃; for 96h;
With ammonium hydroxide In toluene
With ammonia In methanol
With ammonia In methanol at 20℃; for 72h;
19.5 g
Stage #1: methyl (2S)-2-amino-3-phenylpropanoate hydrochloride With sodium hydrogencarbonate In chloroform
Stage #2: With ammonium hydroxide In toluene at 20℃; for 24h;
31 (S)-2-Amino-3-phenylpropanamide 30
To a solution of L-Phenylalanine methyl ester hydrochloride (26.1 g, 121 mmol, 1 eq) in chloroform (200 ml) was added saturated NaHC03 solution until pH paper indicated the solution to be basic. The free amine was extracted with chloroform (2 x 200 ml), dried over MgS04 and evaporated under reduced pressure. The resulting L-Phenylalanine methyl ester was dissolved in toluene (300 ml) and to this solution was added saturated ammonium hydroxide solution (150 ml). The reaction was stirred at room temperature for 24 hours before being evaporated to dryness under reduced pressure. The crude product did not require further purification (19.5 g, 1 19 mmol, 98 %). 1H NMR (400 MHz, DMSO): δ = 1 .90 (brs, 2H, NH2), 2.59 (dd, J = 13.4 Hz, 8.3 Hz, 1 H), 2.92 (dd, J = 13.4 Hz, J = 5.1 Hz, 1 H), 3.34 (dd, J = 8.3 Hz, 5.1 Hz, 1 H), 6.96 (brs, 1 H), 7.16-7.30 (m, 5H), 7.32 (brs, 1 H); 13C NMR (100.6 MHz, CDCI3): δ = 42.0, 57.1 , 126.9, 128.9, 130.2, 139.8, 177.6.
[3-((S)-1-Carbamoyl-2-phenyl-ethylcarbamoyl)-propyl]-carbamic acid benzyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide Ambient temperature;
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide Ambient temperature;
Multi-step reaction with 2 steps
1: methanesulfonic acid / 3 h / Cooling with ice; Reflux
2: ammonium hydroxide / 6 h / 20 °C
Stage #1: L-phenylalanine In ethanol at 78℃; for 16h;
Stage #2: With ammonia at 20℃; for 96h; Autoclave;
1 Example 1:
In a 350-ml four-necked flask equipped with a KPG-stirrer, thermometer, and a reflux condenser with an argon inlet was charged with 10.2 g (60.5mmol) L-phenylalanine, 13.2 g Dowex 50WX8 hydrogen form (dried) and 120 ml ethanol (2055 mmol). The mixture was stirred at 400 rpm and heated at reflux 78°C (100°C oil) for 16 h. The mixture was cooled to room temperature and transferred in a 500 ml autoclave filled with 96 g ammonia. The mixture was stirred at 20°C at 1000 rpm at 6 bar for 4 days. The reaction mixture was sucked out and the Dowex was filtered and washed with ethanol and toluene. The filtrate was evaporated under reduced pressure (10 mbar, 40°C). 10.01 g L-phenylalanine-amide with a yield of 65% with a purity of 64.5% is obtained
8-acetyl-3-(S)-benzyl-1,4,8-triaza-spiro[4.5]decan-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
99%
In ethanol; at 20℃; for 18.5h;Heating / reflux;
Example 7 8-Acetyl-3-(S)-benzyl-1,4,8-triazaspiro[4,5]decan-2-one A solution of 1-acetylpiperidin-4-one (1.5 g, 10.8 mmol) and (S)-phenylalaninamide (1.8 g, 10.8 mmol) in EtOH (30 ml) was heated under reflux for 2.5 h and stirred at RT for a further 16 h. After removal of the solvent and drying in vacuo, the product 8-acetyl-3-(S)-benzyl-1,4,8-triazaspiro[4,5]decan-2-one was obtained in a yield of 3.0 g (99%).
With 4-methyl-morpholine; benzotriazol-1-ol; In methanol; dichloromethane; N,N-dimethyl-formamide;
To 260 mg (0.87 mmol) of the acid above dissolved in 5 ml DMF was added 140 mg (0.85 mmol) L-phenylalaninamide [educt 2], 120 mg (0.88 mmol) of HOBT, 170 mg (0.88 mmol) of EDCI and 0.34 ml (3.06 mmol) of N-methylmorpholine. The reaction mixture was stirred at room temperature overnight, partitioned between ethyl acetate and water, dried over magnesium sulfate and concentrated to give the 388 mg of the crude product as a white solid. To the solution of 388 mg (0.87 mmol) of the crude product from above in dichloromethane (10 ml) was added <strong>[29684-56-8]Burgess Reagent</strong> 210 mg (0.88 mmol). The mixture was stirred at room temperature for overnight. After the dichloromethane was removed, the residue was dissolved in 2 ml MeOH and purified with preparative thin layer chromatography (hexane:ethyl acetate 1:1) to give the product as a white foam: 88 mg (0.21 mmol). 27.5% yield.
(S)-[1,6]naphthyridine-2-carboxylic acid (1-carbamoyl-2-phenyl-ethyl)-amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃;
General method 3; 3 mmol 1,6-naphthyridine carboxylic acid, 3,3 mmol 1-hydroxybenzotriazole, 4,5 mmol of a chiral compound such as R-(+)-1-phenylethylamine and 3,3 mmol N'-(3- dimehylaminopropyl)-N-ethylcarbodiimide hydrochloride was stirred in 100ml abs. DMF overnight at room temperature. 400 ml cold water was added and stirred for additional 1 hour. Extracted with ethyl acetate, washed with NaHCOe, saturated NaCI, dried over MgSO4. The solvent was removed, the yellow oil was chromatogaphed on silica gel eluted with ethylacetate. Yield about 45%
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.25h; Microwave irradiation; Inert atmosphere;
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 20h;
Example 31 (R)-5-(1-amino-1-oxo-3-phenylpropan-2-ylamino)-3-(quinolin-6-ylamino)pyrazine-2-carboxamide A solution of <strong>[313339-92-3]3,5-dichloropyrazine-2-carbonitrile</strong> (86 mg, 0.494 mmol), D-phenylalaninamide (81 mg, 0.494 mmol) and DIEA (0.130 mL, 0.747 mmol) in DMF (2 mL) was stirred at room temperature for 20 h. Water and EtOAc were added. Organic phase was separated, washed with 1N HCl, then with 5% NaHCO3, dried over Na2SO4, concentrated in vacuo to give (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)-3-phenylpropanamide (128 mg) as an oil.
(S)-2-(3,5-dichloropyridin-2-ylamino)-3-phenylpropionamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 48h;Inert atmosphere;
General procedure: To an oven-dry ground test tube equipped with a stir bar were added 1 mmol 2-bromoiodobenzene, 1mmolL-alaninamide, 3 mmol potassium carbonate and 5 mL DMF. The test tube was sealed with a rubber stopperand was evacuated and refilled with argon for three times. Then the test tube was stirred in an oil bathpreheated at 90? C for 48 hours. After the test tube was cooled to room temperature, the reaction wasquenched with water, and the reaction mixture was extracted with 20 mL ethyl acetate for three times. Thecombined organic layer was washed with 10 mL water and then saturated sodium chloride aqueous solution,and dried over anhydrous sodium sulfate. After filtration, the filtrate was condensed on a rotary evaporator invacuum. The resulting crude product was chromatographed on silica gel (300-400 mesh) with a 1:2 volumeratio mixed solution of ethyl acetate and petroleum ether as eluent to give a white solid L-N-phenylalaninamide.
(S)-2-(2-chloro-5-methoxyphenylamino)-3-phenylpropionamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 48h;Inert atmosphere;
General procedure: To an oven-dry ground test tube equipped with a stir bar were added 1 mmol 2-bromoiodobenzene, 1mmolL-alaninamide, 3 mmol potassium carbonate and 5 mL DMF. The test tube was sealed with a rubber stopperand was evacuated and refilled with argon for three times. Then the test tube was stirred in an oil bathpreheated at 90? C for 48 hours. After the test tube was cooled to room temperature, the reaction wasquenched with water, and the reaction mixture was extracted with 20 mL ethyl acetate for three times. Thecombined organic layer was washed with 10 mL water and then saturated sodium chloride aqueous solution,and dried over anhydrous sodium sulfate. After filtration, the filtrate was condensed on a rotary evaporator invacuum. The resulting crude product was chromatographed on silica gel (300-400 mesh) with a 1:2 volumeratio mixed solution of ethyl acetate and petroleum ether as eluent to give a white solid L-N-phenylalaninamide.
(S)-3-phenyl-2-(2,4,5-tribromophenylamino)propionamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With copper(l) iodide; potassium carbonate In N,N-dimethyl-formamide at 120℃; for 48h; Inert atmosphere;
Typical Procedure for CuI-catalyzed selective C-N coupling
General procedure: To an oven-dry ground test tube equipped with a stir bar were added 1 mmol 2-bromoiodobenzene, 1mmolL-alaninamide, 3 mmol potassium carbonate and 5 mL DMF. The test tube was sealed with a rubber stopperand was evacuated and refilled with argon for three times. Then the test tube was stirred in an oil bathpreheated at 90∘ C for 48 hours. After the test tube was cooled to room temperature, the reaction wasquenched with water, and the reaction mixture was extracted with 20 mL ethyl acetate for three times. Thecombined organic layer was washed with 10 mL water and then saturated sodium chloride aqueous solution,and dried over anhydrous sodium sulfate. After filtration, the filtrate was condensed on a rotary evaporator invacuum. The resulting crude product was chromatographed on silica gel (300-400 mesh) with a 1:2 volumeratio mixed solution of ethyl acetate and petroleum ether as eluent to give a white solid L-N-phenylalaninamide.
(S)-2-((6-bromo-4-methyl-3-oxo-3,4-dihydropyrazin-2-yl)amino)-3-phenylpropanamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 80℃; for 5h;
General procedure: To a solution of 2a-j (10 mmol, 1.0 eq) , <strong>[87486-34-8]3,5-dibromo-1-methylpyrazin-2(1H)-one</strong> (2.95 g, 11 mmol, 1.1 eq) and DIEA (3.3 mL,20 mmol, 2.0 eq) in MeCN (20mL) was stirred at 80 °C for 5 hours. After cooling to room temperature, thesolvent was removed in vacuo, and the residue was purified using silica gelchromatography to give the title compounds, yield 72-85percent.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
