* 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.
With ammonium formate In methanol at 20℃; for 48 h;
A mixture of 2-benzylaminoquinoxaline (1.30 g, 5.50 mmol), ammonium formate (3.13 g, 49.7 mmol) and Pd-C (10percent Pd, 130 mg) in MeOH (60 mL) was stirred at . rt for 48 h. The mixture was filtered through Celite.(R)., concentrated and purified by chromatography to give the title compound (278 mg, 25percent) as an orange oil. 1H NMR (DMSO-J6, 400 MHz) δ 8.26 (s, IH), 7.74 (d, IH), 7.55-7.46 (m, 2H), 7.30 (ddd, IH), 6.95 (s, 2H).
Step 1: To 2-chloroquinoxaline (1.0 g, 6 mmol) was added ammonia in methanol (8 mL of a 2M solution). The reaction was sealed in a vial, heated to 80° C., and stirred for 12 hours. The reaction was cooled to room temperature and concentrated under reduced pressure. The residue was taken up in methylene chloride and filtered. Hexane was added until a precipitate formed which was filtered and found to be the desired product (5percent yield).
Reference:
[1] Angewandte Chemie - International Edition, 2015, vol. 54, # 12, p. 3773 - 3777[2] Angew. Chem., 2015, vol. 127, # 12, p. 3844 - 3848,5
[3] Organic Letters, 2013, vol. 15, # 14, p. 3734 - 3737
[4] Tetrahedron, 2010, vol. 66, # 34, p. 6958 - 6964
[5] Patent: US2003/69284, 2003, A1,
[6] Journal of the Chemical Society, 1945, p. 622,625
[7] Patent: US2537870, 1946, ,
3
[ 34117-90-3 ]
[ 829-85-6 ]
[ 5424-05-5 ]
[ 1422239-76-6 ]
[ 4559-70-0 ]
[ 1101-41-3 ]
Yield
Reaction Conditions
Operation in experiment
45%
Stage #1: at 130℃; for 2 h; Inert atmosphere; Schlenk technique Stage #2: With potassium hydroxide In diethyl ether; water
Heating a mixture of 2a (495 mg, 2.75 mmol) and Ph2PH (0.48 mL, 2.76 mmol) in the presence of Pd(OAc)2 (0.8 mg, 0.13 molpercent) for 2 h at 130°C led to a viscous blue-green mass. Extraction of the soluble part with diethyl ether and NMR monitoring in C6D6 identified Ph2P-PPh2, Ph2PCl, 3a and an unknown phosphorus compound (31P signals at d 14.9, 82.2, 12.8 and 5.4 ppm, intensity ratio 84:12:2:2). The insoluble hydrochloride part, 615 mg blue-green powder, was treated with aqueous NaOH/Et2O. The ether phase was dried with Na2SO4 and the ether removed in vacuo to give a brownish-yellow viscous mass (220 mg) with a low content of 3a (relative 31P intensity ca. 20percent besides signals of Ph4P2, Ph2PHO and other P compounds). Purification under aerobic conditions by column chromatography on silica gel (ethyl acetate/hexane 95/5percent) and removal of solvent gave 180 mg (45percent) pale yellow solid 2-aminoquinoxaline. Mp: 156°C. 1H NMR (CDCl3) d: 5.03 (vbr s, 2H, NH2), 7.45 (td, 3J = 8.4, 7, 4J = 1.2 Hz, 1H, H-6), 7.61 (td, 3J = 8.4, 7, 4J = 1.2 Hz, 1H, H-7), 7.67 (dd, 3J = 8.4, 4J = 1.2 Hz, 1H, H-8), 7.92 (dd, 3J = 8.4, 4J = 1.2 Hz, 1H, H-5), 8.35 (s, 1H, H-3); these values are in good agreement with the reported data [17]. 13C NMR (CDCl3) d: 125.05 (CH-6), 125.88 (CH-8), 128.83 (CH-5), 137.43 (Cq-4a), 137.78 (CH-3), 130.29 (CH-7), 140.89 (Cq-8a), 151.97 (Cq-2). HRMS (ESI in MeOH): Calc. for C8H7N3 [M+H+] 146.0713; found: 146.0713.
Reference:
[1] Journal of the Chemical Society, 1945, p. 622,625
[2] Journal of the American Chemical Society, 1951, vol. 73, p. 4955
[3] Journal of the American Chemical Society, 1951, vol. 73, p. 4955
[4] Patent: US2537870, 1946, ,
[5] Journal of the Chemical Society, 1945, p. 622,625
6
[ 60093-60-9 ]
[ 5424-05-5 ]
Reference:
[1] Journal of the American Chemical Society, 1951, vol. 73, p. 4955
[2] Journal of the American Chemical Society, 1951, vol. 73, p. 4955
[3] Patent: US2650221, 1951, ,
[4] Patent: US2650221, 1951, ,
7
[ 490-59-5 ]
[ 5424-05-5 ]
Reference:
[1] Journal of the Chemical Society, 1956, p. 26,27
[2] Journal of the American Chemical Society, 1944, vol. 66, p. 1957
[3] Journal of the American Chemical Society, 1944, vol. 66, p. 1957
With ammonia; In methanol; hexane; dichloromethane;
Step 1: To <strong>[1448-87-9]2-chloroquinoxaline</strong> (1.0 g, 6 mmol) was added ammonia in methanol (8 mL of a 2M solution). The reaction was sealed in a vial, heated to 80 C., and stirred for 12 hours. The reaction was cooled to room temperature and concentrated under reduced pressure. The residue was taken up in methylene chloride and filtered. Hexane was added until a precipitate formed which was filtered and found to be the desired product (5% yield).
With ammonium formate In methanol at 20℃; for 48h;
b
A mixture of 2-benzylaminoquinoxaline (1.30 g, 5.50 mmol), ammonium formate (3.13 g, 49.7 mmol) and Pd-C (10% Pd, 130 mg) in MeOH (60 mL) was stirred at . rt for 48 h. The mixture was filtered through Celite, concentrated and purified by chromatography to give the title compound (278 mg, 25%) as an orange oil. 1H NMR (DMSO-J6, 400 MHz) δ 8.26 (s, IH), 7.74 (d, IH), 7.55-7.46 (m, 2H), 7.30 (ddd, IH), 6.95 (s, 2H).
1.A
EXAMPLE 1; l-r2-(3-Amino-propoxyV5-chloro-phenyll-3-(4-oxy-quinoxalin-2-yl')-urea Step A: Quinoxalin-2-ylamine (1.72 mmol) was dissolved in pyridine (10 ml) and a catalytic amount of DMAP was added followed by addition of 1.2 equivalents of phenylchloroformate. The reaction was stirred at room temperature for 2 hours. The solvent was removed by evaporation and purified by column chromatography eluting 30-50% ethyl acetate/hexanes.
517.A Preparation of 'N-(2-Chloro-6-methylphenyl)-2-(2-quinoxalinylamino)-5-thiazolecarboxamide
[0557] Compound 517A was prepared from 473A by an analogous method as that of 473B, except using 2-aminoquinoxaline in place of 2-bromo-6-aminopyridine.
2-fluoro-5-methoxyphenylglyoxal monohydrate[ No CAS ]
[ 7732-18-5 ]
[ 174266-69-4 ]
Yield
Reaction Conditions
Operation in experiment
In hydrogenchloride
X EXAMPLE X STR20
EXAMPLE X STR20 A solution of 2-aminoquinoxaline (100 mg) and 2-fluoro-5-methoxyphenylglyoxal monohydrate (150 mg) in 5% HCl (6 mL) was heated to 60°-65° C. for 8 h. After cooling the mixture to room temperature the precipitate which had formed during the reaction was collected via suction filtration and washed with 5% HCl (1*) followed by H2 O (3*). The product was then washed with methylene chloride and dried. The above procedure provided 2-(2-fluoro-5-methoxyphenyl)-imidazo-[1,2-a]quinoxalin-1(5H)-one (Compound 30) as a brick-red solid, mp 318°-320° C.
6-[8-(quinoxalin-2-ylamino)-pyrido[2,3-b]pyrazin-3-yl]-5-trifluoromethyl-nicotinamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
at 140℃; for 20h;
2.K.2
2. 6-(8-(Quinoxalin-2-ylamino)pyrido[2,3-b]pyrazin-3-yl)-5-(trifluoromethyl)nicotinamideHeat a mixture of 6-(8-chloropyrido[2,3-b]pyrazin-3-yl)-5-(trifluoromethyl)nicotinamide (70.6 mg, 0.2 mmol) and 2-aminoquinoxaline (85.8 mg, 0.6 mmol) in a screw cap vial at 1400C for 20 hours under N2 atmosphere. Purify the reaction mixture by column chromatography using 1-2% MeOH / EtOAc as eluent to afford the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 11.017 (s, IH), 9.461 (s, 2H), 9.335 (d, IH, J=I.1 Hz), 9.307 (s, IH), 9.129 (d, IH, J=I .3 Hz), 8.836 (s, IH), 8.557(s, IH), 7.975 (m, 3H), 7.789 (t, IH), 7.647(t, IH). MS = 463.12 (M+H). The IC50 determined as described in Example 6 is less than 1 micromolar.
1-carbethoxy-carbonylmethyl-2-amio-quinoxalinium bromide[ No CAS ]
[ 76577-81-6 ]
Yield
Reaction Conditions
Operation in experiment
In 1,2-dimethoxyethane
1.A STEP A:
STEP A: 1-carbethoxy-carbonylmethyl-2-amio-quinoxalinium bromide A solution of 0.9 g of 2-amino-quinoxaline, 1.25 g of ethyl bromopyruvate and 25 ml of dimethoxyethane was stirred overnight at room temperature and was filtered to recover 1.58 g of 1-carbethoxy-carbonylmethyl-2-amino-quinoxalinium bromide as a pale yellow crystalline solid.
methoxymethylene-isopropylidene malonate[ No CAS ]
N-(2'-quinoxalinyl)-aminomethylene-isopropylidene malonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
In methanol
1.A STEP A:
STEP A: N-(2'-quinoxalinyl)-aminomethylene-isopropylidene malonate A solution of 2.0 g of methoxymethylene-isopropylidene malonate in 40 ml of methanol was added to a solution of 2.0 g of 2-aminoquinoxaline in 40 ml of methanol and a white precipitate formed which was filtered off and washed with methanol to obtain 2.8 g of N-(2'-quinoxalinyl)-aminomethylene-isopropylidene malonate (68% yield).
(trans)-2-oxo-3-phenyl-1-oxa-3-azaspiro[4.5]decane-8-carboxylic acid[ No CAS ]
trans-2-oxo-3-phenyl-N-2-quinoxalinyl-1-oxa-3-azaspiro[4.5]decane-8-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Stage #1: (trans)-2-oxo-3-phenyl-1-oxa-3-azaspiro[4.5]decane-8-carboxylic acid With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 20℃; for 1.5h;
Stage #2: quinoxalin-2-ylamine In 1,4-dioxane at 80℃; for 20h;
6.1
Example 6; Example 6-1; (Trans)-2-oxo-3-phenyl-λ/-2-quinoxalinyl-1-oxa-3-azaspiro[4.51decane-8-carboxamide hydrochloride; DIPEA (0.048 ml_, 0.272 mmol) and propylphosphonic anhydride (0.106 ml_, 0.182 mmol) were added to a solution of (trans)-2-oxo-3-phenyl-1-oxa-3-azaspiro[4.5]decane-8- carboxylic acid (prepared in an analogous way to Intermediate 14 procedure 14b, 50 mg, 0.182 mmol) in 1 ,4-dioxane (1.5 ml) and stirred at room temperature for 1.5 h. Then 2- quinoxalinamine (26.4 mg, 0.182 mmol) in 1 ,4-dioxane (1 ml) was added and the resulting solution was stirred at 8O0C for 20 hrs. Solvent was evaporated and the crude obtained dissolved in dichloromethane and washed twice with H2O. The organic phases were collected, dried over Na2SO4 and the dichloromethane was evaporated. The crude obtained was purified with Biotage SP1 , over a 12M Silica cartridge, eluting with a mixture cyclohexane/EtOAc. (trans)-2-oxo-3-phenyl-N-2-quinoxalinyl-1-oxa-3-azaspiro[4.5]- decane-8-carboxamide was eluted with 40% EtOAc (4 mg).1H NMR (400 MHz, CDCI3): δ 9.85 (s, 1 H), 8.2 (brs, 1 H), 8.15-8.10 (m, 1 H), 7.87-7.85 (m,1 H), 7.78-7.69 (m, 2H), 7.61-7.56 (m, 2H), 7.44-7.39 (m, 2H), 7.20-7.15 (m, 1 H), 3.86 (2H, s), 2.53-2.70 (1 H, m), 2.05-2.34 (4H, m), 1.85-2.02 (4H, m).UPLC-MS: 0.73 min, 403 [M+H]+.
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,2-dimethoxyethane for 17h; Reflux; regioselective reaction;
Stage #1: 2,3-dibromopyridine; quinoxalin-2-ylamine With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,2-dimethoxyethane Reflux;
Stage #2: With (±)-1,2-trans.-cyclohexanediamine; copper(l) iodide In 1,2-dimethoxyethane for 8h; Reflux;
Stage #1: quinoxalin-2-ylamine; 2-chloro-3-iodopyridine With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,2-dimethoxyethane for 17h; Reflux;
Stage #2: With (±)-1,2-trans.-cyclohexanediamine In 1,2-dimethoxyethane for 8h; Reflux;
Stage #1: quinoxalin-2-ylamine; 2-chloro-3-iodopyridine With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene for 17h; Reflux;
Stage #2: With (±)-1,2-trans.-cyclohexanediamine; copper(l) iodide In toluene for 8h; Reflux;
Stage #1: quinoxalin-2-ylamine; 2-chloro-3-iodopyridine With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,2-dimethoxyethane for 17h; Reflux;
Stage #2: With (±)-1,2-trans.-cyclohexanediamine; copper(l) iodide In 1,2-dimethoxyethane for 8h; Reflux;
Heating a mixture of 2a (495 mg, 2.75 mmol) and Ph2PH (0.48 mL, 2.76 mmol) in the presence of Pd(OAc)2 (0.8 mg, 0.13 mol%) for 2 h at 130C led to a viscous blue-green mass. Extraction of the soluble part with diethyl ether and NMR monitoring in C6D6 identified Ph2P-PPh2, Ph2PCl, 3a and an unknown phosphorus compound (31P signals at d 14.9, 82.2, 12.8 and 5.4 ppm, intensity ratio 84:12:2:2). The insoluble hydrochloride part, 615 mg blue-green powder, was treated with aqueous NaOH/Et2O. The ether phase was dried with Na2SO4 and the ether removed in vacuo to give a brownish-yellow viscous mass (220 mg) with a low content of 3a (relative 31P intensity ca. 20% besides signals of Ph4P2, Ph2PHO and other P compounds). Purification under aerobic conditions by column chromatography on silica gel (ethyl acetate/hexane 95/5%) and removal of solvent gave 180 mg (45%) pale yellow solid 2-aminoquinoxaline. Mp: 156C. 1H NMR (CDCl3) d: 5.03 (vbr s, 2H, NH2), 7.45 (td, 3J = 8.4, 7, 4J = 1.2 Hz, 1H, H-6), 7.61 (td, 3J = 8.4, 7, 4J = 1.2 Hz, 1H, H-7), 7.67 (dd, 3J = 8.4, 4J = 1.2 Hz, 1H, H-8), 7.92 (dd, 3J = 8.4, 4J = 1.2 Hz, 1H, H-5), 8.35 (s, 1H, H-3); these values are in good agreement with the reported data [17]. 13C NMR (CDCl3) d: 125.05 (CH-6), 125.88 (CH-8), 128.83 (CH-5), 137.43 (Cq-4a), 137.78 (CH-3), 130.29 (CH-7), 140.89 (Cq-8a), 151.97 (Cq-2). HRMS (ESI in MeOH): Calc. for C8H7N3 [M+H+] 146.0713; found: 146.0713.
b) Without Pd-catalyst and base - detection of 2-aminoquinoxaline and 3a: Compound 2a (120 mg, 0.65 mmol) was heated with Ph2PH (0.11 mL, 0.64 mmol) for 1.5h at 130 C. Then the resulting blue viscous substance was extracted with diethyl ether to give an olive-green powder (186 mg). The filtrate displayed 31P NMR signals of Ph2PH, Ph4P2 and 3a, signal intensities 31:61:5. An aliquot (90 mg) of the powder was treated with Et2O / aqueous NaOH. Phase separation and drying over CaCl2 gave ca. 50 mg of a viscous yellow mixture of 3a and 2-aminoquinoxaline (13CH signal intensities 1:1), contaminated by small amounts of unconverted Ph2PH and unidentified side products. The 13C NMR data of 3a are in good agreement with those of the pure product. - 2-Aminoquinoxaline: The 1H NMR data are in good agreement with reported values [5]. 13C NMR (CDCl3): d 151.97 (Cq-2), 140.89 (Cq-8a), 137.78 (CH-3), 137.43 (Cq-4a), 130.29 (CH-7), 128.83 (CH-5), 125.88 (CH-8), 125.05 (CH-6); HRMS (ESI in MeOH): Calcd. for 2-aminoquinoxaline (C8H7N3) [M+H+] 146.0713; found: 146.0713; calcd. for 3a (C20H16N3P) [M+H+] 330.1155; found: 330.1158.
7
2-Aminoquinoxaline (710.5 mg, 4.9 mmol) was added to a round bottom flask.After pyridine (2mL),Add 1-chlorosulfonyl-4-acetamidobenzene-d4 (1.2 g, 5.1 mmol),Not more than 55 reaction 1h.Aqueous sodium hydroxide (5 M, 1.5 mL) was slowly added and heating was continued for 30 min.After removing the pyridine under reduced pressure, water was added and filtered.The filter cake was recrystallized from glacial acetic acid to give sulfaquinoxaline-d4 (387.7mg, 26%, purity 99.5% (HPLC), abundance 99.5% (atom%, HRMS)).
phenyl (6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)carbamic acid ester[ No CAS ]
1-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(quinoxaline-2-yl)urea[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
2.7 mg
With triethylamine In N,N-dimethyl-formamide at 50℃;
1 End product 269: 1- (6- (4-isopropyl-4H-1,2,4-triazol-3-yl) pyridin-2-yl) -3- (quinoxaline-2-yl) urea (269, YC117)
The final product 03 (20 mg, 0.062 mmol), 2-aminoquinoxaline (26 mg, 0.186 mmol) and Et3N (25 mg, 0.25 mmol) were weighed into a bottle, and 2 mL of DMF was added to dissolve the reaction reagent. The reaction was heated at 50 ° C overnight. The crude reaction product was directly purified by reverse-phase HPLC to obtain the target compound YC117 (2.7 mg).
phenyl (R)-(6-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl) carbamate[ No CAS ]
(R)-1-(6-(4-(1-hydroxyprop-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(quinoxaline-2-yl)urea[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
3.1 mg
With triethylamine In N,N-dimethyl-formamide at 50℃;
1 Final product 323: (R) -1- (6- (4- (1-hydroxyprop-2-yl) -4H-1,2,4-triazol-3-yl) pyridin-2-yl) -3 -(Quinoxaline-2-yl) urea (YD060)
2-Aminoquinoxaline (26 mg, 0.18 mmol), YD040 (30 mg, 0.088 mmol) and Et3N (36 mg, 0.35 mmol) were weighed into a bottle, and DMF was added to dissolve the reaction reagent. The reaction was heated at 50 ° C overnight.The crude reaction product was directly purified by reverse-phase HPLC to obtain the target compound YD060 (3.1 mg).
phenyl (6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)carbamic acid ester[ No CAS ]
[ 76-05-1 ]
(x)C2HF3O2*C19H18N8O[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
8%
Stage #1: quinoxalin-2-ylamine; phenyl (6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)carbamic acid ester With triethylamine In N,N-dimethyl-formamide at 50℃; for 12h;
Stage #2: trifluoroacetic acid In water; acetonitrile
1-(6-(4-Isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(pyridin-2-yl)urea (11h)
General procedure: General Method B: 11c (30mg, 0.0929mmol), pyridin-2-amine (26mg, 0.28mmol), and Et3N (38mg, 0.37mmol) were placed in a round-bottom flask, followed by addition of DMF (2mL). The mixture was heated up at 50°C for 12h. Water (4mL) was added and the mixture was purified by reverse phase HPLC to afford 11h as a solid of TFA salt (22.9mg, 56%).
phenyl (R)-(6-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl) carbamate[ No CAS ]
[ 76-05-1 ]
(x)C2HF3O2*C19H18N8O2[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
8%
Stage #1: quinoxalin-2-ylamine; phenyl (R)-(6-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl) carbamate With triethylamine In N,N-dimethyl-formamide at 50℃; for 12h;
Stage #2: trifluoroacetic acid In water; acetonitrile
1-(6-(4-Isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(pyridin-2-yl)urea (11h)
General procedure: General Method B: 11c (30mg, 0.0929mmol), pyridin-2-amine (26mg, 0.28mmol), and Et3N (38mg, 0.37mmol) were placed in a round-bottom flask, followed by addition of DMF (2mL). The mixture was heated up at 50°C for 12h. Water (4mL) was added and the mixture was purified by reverse phase HPLC to afford 11h as a solid of TFA salt (22.9mg, 56%).
6-chloro-3,4-dihydro-1H-1,7-naphthyridin-2-one[ No CAS ]
6-(quinoxalin-2-ylamino)-3,4-dihydro-1H-1,7-naphthyridin-2-one hydrochloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
5 mg
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 120℃; for 12h;
59.4
To the mixture of quinoxalin-2-amine (27.82 mg, 191.67 umol, 1 eq) and 6-cliloro-3,4-dihydro-1H-1,7-naphthyridin-2-one (35 mg, 191.67 umol, 1 eq) in dioxane (5 mL) was added Pd2(dba)3 (17.55 mg, 19.17 umol, 0.1 eq), Cs2CO3 (187.35 mg, 575.01 umol, 3 eq) and Xantphos (11.09 mg, 19.17 umol, 0.1 eq). The mixture was stirred at 120 °C for 12 hr. The mixture was filtered. The filter cake was washed with EtOAc (50 mL). The filtrate was concentrated in vacuum. The residue was purified by prep-HPLC (column: Phenomenex Luna C18 100 *30mm *5 um; mobile phase: [water (0.04%HCl)-ACN]; B%: 10%-40%, 10min). 6-(qumoxalin-2-ylamino)-3,4-dihydro-1H-1,7-naphthyridin-2-one (5 mg, HCl salt, 100% purity) was obtained. LCMS: (M+H)+ : 292.1.
N-[(pyridin-3-yl)methyl]quinoxalin-2-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
30%
Stage #1: 3-pyridinecarboxaldehyde; quinoxalin-2-ylamine In toluene at 120℃; for 24h; Molecular sieve;
Stage #2: With sodium tetrahydroborate; ethanol In toluene at 70℃; for 0.5h;
141.1 Preparation of N-[(pyridin-3-yl)methyl]quinoxalin-2-amine
In a reaction vial, a solution of pyridine-3-carbaldehyde (0.097 mL, 1.0 mmol) and quinoxalin-2- amine (150 mg, 1.0 mmol) in dry toluene (5.2 mL) was stirred at 100 °C with activated 4 Å molecular sieves under nitrogen overnight. The reaction mixture was cooled to 60 °C and then poured into a suspension of sodium borohydride (194 mg, 5.2 mmol) in dry ethyl alcohol (5.2 mL). The reaction mixture was stirred at 70 °C for 30 minutes and then cooled to room temperature. The reaction was filtered over a bed of Celite and washed with ethyl acetate (2x 20 mL). The filtrate was concentrated then diluted with dichloromethane and filtered again. The filtrate was purified via flash column chromatography eluting with 0-10% methanol in dichloromethane. Product N-[(pyridin-3-yl)methyl]quinoxalin-2-amine (106 mg, 0.45 mmol, 44 %) was afforded as a beige solid.1H NMR (300 MHz, Chloroform-d) δ 8.71 (d, J = 2.3 Hz, 1H), 8.56 (dd, J = 4.9, 1.7 Hz, 1H), 8.25 (s, 1H), 7.90 (dd, J = 8.2, 1.5 Hz, 1H), 7.83 - 7.69 (m, 2H), 7.60 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H), 7.43 (ddd, J = 8.3, 7.0, 1.5 Hz, 1H), 7.38 - 7.20 (m, 1H), 5.29 (s, 1H), 4.80 (d, J = 5.8 Hz, 2H); LCMS (ESI) m/z: 237.1 [M+H]+.
N-[(pyridin-3-yl)methyl]-N-(quinoxalin-2-yl)cyclohexanecarboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Multi-step reaction with 2 steps
1.1: toluene / 24 h / 120 °C / Molecular sieve
1.2: 0.5 h / 70 °C
2.1: triethylamine / tetrahydrofuran / 1.5 h / 20 °C