* 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.
(i) 2-Amino-3-bromo-5-methylpyrazine (0.374 g) was added to a freshly prepared solution of sodium methoxide in methanol (made by addition of sodium (0.115 g) to methanol (6 ml)). The reaction was heated under reflux for 18 hours, cooled to ambient temperature and the solvent removed by evaporation. Water (5 ml) was added to the residue and extracted with dichloromethane (3*20 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by chromatography on silica gel, eluding with dichloromethane to give 2-amino-3-methoxy-5-methylpyrazine as a white crystalline solid (0.208 g, 75percent), m.p. 67°-69° C.; mass spectrum (+ve CI): 140 (M+H)+.
75%
With sodium methylate; sodium In methanol; water
(b) 2-Amino-3-bromo-5-methylpyrazine (0.374 g) was added to a freshly prepared solution of sodium methoxide in methanol (made by addition of sodium (0.115 g) to methanol (6 ml)). The reaction was heated under reflux for 18 hours, cooled to ambient temperature and the solvent removed by evaporation. Water (5 ml) was added to the residue and extracted with dichloromethane (3*20 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by chromatography on silica gel, eluding with dichloromethane to give 2-amino-3-methoxy-5-methylpyrazine as a white crystalline solid (0.208 g, 75percent), m.p. 67°-69° C.; mass spectrum (+ve CI): 140 (M+H)+.
75%
With sodium methylate; sodium In methanol; water
(ii) 2-Amino-3-bromo-5-methylpyrazine (0.374 g) was added to a freshly prepared solution of sodium methoxide in methanol (made by addition of sodium (0.115 g) to methanol (6 ml). The reaction mixture was heated under reflux for 18 hours, cooled to ambient temperature and the solvent removed by evaporation. Water (5 ml) was added to the residue and extracted with dichloromethane (3*20 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by chromatography on silica gel, eluding with dichloromethane to give 2-amino-3-methoxy-5-methylpyrazine as a white crystalline solid (0.208 g, 75percent), m.p. 67°-69° C.; mass spectrum (+ve CI): 140 (M+H)+.
Reference：
[1] Patent: US5861401, 1999, A,
[2] Patent: US5866568, 1999, A,
[3] Patent: US5668137, 1997, A,
2
[ 67-56-1 ]
[ 124-41-4 ]
[ 74290-65-6 ]
[ 89464-87-9 ]
Yield
Reaction Conditions
Operation in experiment
92%
at 30 - 100℃; for 6 h; Inert atmosphere
[00791] To a mixture of 3-bromo-5-methyl-pyrazin-2-amine (31 g, 164.87 mmol) in MeOH (150 mL) was added NaOMe (14 g, 263.79 mmol) in one portion at 30 °C under N2. The mixture was stirred at 100 °C for 6 hrs. The mixture was concentrated under reduced pressure and the resulting residue was dissolved in water (100 mL). The mixture was extracted with EtOAc and the combined organic layers were washed with brine (20 mL), dried with Na2S04, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (to afford 3-methoxy-5-methyl-pyrazin-2-amine (21 g, 92percent yield) as a white solid. 1H MR (400 MHz, CDCh-d) δ ppm 7.39 (s, 1H) 4.59 (br s, 2 H) 3.97 (s, 3 H) 2.29 (s, 3 H)
3,4,5-trichloro-N-(3-methoxy-5-methylpyrazin-2-yl)thiophene-2-sulphonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
<strong>[89464-87-9]3-methoxy-5-methylpyrazin-2-amine</strong> (0.33 g) and the product of Example 1, step (a) were subjected to the procedure described in Example 1, step (b) to afford the product as a pale yellow solid (0.68 g).m/e 389 (M+l)+, 100%.JH NMR (CDC13) 8 7.8 (1H, br), 7.58 (1H, br), 4.01 (3H, s), 2.35 (3H, s).MP 146-147C.Elemental Analysis:Theory: C 30.90, H 2.07, N 10.81 %Found: C 31.12, H 2.00, N 10.79 %
N-(3-Methoxy-5-methyl-2-pyrazinyl)-2-bromobenzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
A. N-(3-Methoxy-5-methyl-2-pyrazinyl)-2-bromobenzenesulfonamide <strong>[89464-87-9]2-amino-3-methoxy-5-methylpyrazine</strong> (1.50 g, 10.8 mmol; synthesised according to Bradbury, R. H., et. al. J. Med. Chem. 1997, 40, 996-1004) and 2-bromobenzenesulfonyl chloride (2.80 g, 11.0 mmol) were reacted according to the procedure of Example 25, Step A. 44A was a pink solid, 2.0 g (52%).
2-chloro-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With pyridine; In dichloromethane;
(i) 4-Dimethylaminopyridine (0.1 g) was added to a solution of 2-chloropyridine-3-sulphonyl chloride (1.06 g), <strong>[89464-87-9]2-amino-3-methoxy-5-methylpyrazine</strong> (0.695 g) and pyridine (0.424 ml) in dichloromethane (5 ml) and the mixture was stirred at ambient temperature for 18 hours. The solution was then transferred to a silica gel Mega Bond Elut column. Elution with 0-40% ethyl acetate/hexane gave 2-chloro-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (0.47 g) as an oil; 1 H NMR (d6 -DMSO): 2.3 (s, 3 H), 3.9 (s, 3 H), 7.5 (s, 1 H), 7.65 (dd, 1 H), 8.45 (dd, 1 H), 8.7 (dd, 1 H); mass spectrum (+ve CI): 315 (M+H)+.
c) Isobutylchloroformate (4.79 ml) was added to a stirred solution of <strong>[89464-87-9]2-amino-3-methoxy-5-methylpyrazine</strong> (5 g) and pyridine (2.91 ml) in dichloromethane (10 ml) at ambient temperature. After 90 minutes the reaction mixture was diluted with dichloromethane (10 ml) and washed with 2M hydrochloric acid (3*20 ml), water (20 ml) and saturated sodium chloride solution (20 ml) and then dried (MgSO4). Volatile material was removed by evaporation to give a solid which was recrystallized from hexane to give isobutyl N-(3-methoxy-5-methylpyrazin-2-yl)carbamate (6.5 g); 1 H NMR (CDCl3): 1.0 (d, 6 H), 2.0 (m, 1 H), 2.4 (s, 3 H), 4.0 (d, 2 H), 4.02 (s, 3 H), 7.3 (s, 1 H), 7.8 (s, 1 H); mass spectrum (positive chemical ionisation (+ve CI)): 240 (M+H)+.
N-(3-methoxy-5-methyl-2-pyrazinyl)-2-iodobenzenesulphonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In pyridine; water;
(i) 2-Iodobenzenesulphonyl chloride (obtained as described in J Org Chem, 1977, 42, 3265) (12.1 g) was added to a solution of <strong>[89464-87-9]2-amino-3-methoxy-5-methylpyrazine</strong> (5.6 g) in pyridine (100 ml) and the solution was heated at 70 C. for 8 hours. Volatile material was removed by evaporation and water (200 ml) was added to the residue. The mixture was extracted with ethyl acetate (2*200 ml) and the extracts were washed with 2M hydrochloric acid (200 ml) and water (200 ml). The extracts were dried (MgSO4) and the solvent was removed by evaporation. The residue was triturated with ether to give N-(3-methoxy-5-methyl-2-pyrazinyl)-2-iodobenzenesulphonamide (7.2 g), m.p. 136-138 C.; 1 H NMR (d6 -DMSO): 2.3 (s,3H), 3.9 (s,3H), 7.3 (dt,1H), 7.5-7.65 (m,2H), 8.05-8.15 (m,2H), 10.7-10.8 (br s, 1H).
4-chloro-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In N,N-dimethyl-formamide;
(i) 2-Amino-3-methoxy-5-methylpyrazine (0.346 g) was added to a suspension of sodium hydride (60% dispersion in oil; 0.25 g) in DMF (10 ml). After 30 minutes 4-chloropyridine-3-sulponyl chloride (0.58 g) (obtained by the procedure described in Ann. Pharm. Fr., 1973, 31, 467) was added as a solid, washed in with DMF (1 ml). The mixture was stirred at ambient temperature for a further 2 hours and was then poured into IM sodium hydrogen sulphate solution (100 ml) and extracted with ethyl acetate (2*100 ml). The organic layers were washed with water (2*100 ml) and saturated sodium chloride solution then combined and dried (MgSO4). Volatile material was removed by evaporation and the residue was purified by gradient elution with 30-50% ethyl acetate/hexane through a silica gel Mega Bond Elut column followed by recrystallisation from ethyl acetate/hexane to give 4-chloro-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (0.117 g) which decomposed without melting about 130 C.; 1 H NMR (d6 -DMSO): 2.3 (d, 3 H), 4.0 (s, 3 H), 8.2 (d, 1 H), 8.5 (d, 1 H), 9.0 (d, 1 H), 9.2 (s, 1 H); mass spectrum (+ve ESP): 315 (M+H)+.
4'-isobutyl-3'-nitro-2-biphenylsulphonyl chloride[ No CAS ]
[ 89464-87-9 ]
4'-isobutyl-N-(3-methoxy-5-methyl-2-pyrazinyl)-3'-nitro-2-biphenylsulphonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In pyridine;
EXAMPLE 66 4'-Isobutyl-3'-nitro-2-biphenylsulphonyl chloride (0.353 g) was added to a solution of <strong>[89464-87-9]2-amino-3-methoxy-5-methylpyrazine</strong> (0.139 g) in pyridine (10 ml) at 0 C. The solution was heated at 75 C. for 18 hours and then volatile material was removed by evaporation. The residue was purified by elution with dichloromethane through a silica gel Mega Bond Elut column and the resulting foam was triturated with ether/hexane (1:1 v/v) to give 4'-isobutyl-N-(3-methoxy-5-methyl-2-pyrazinyl)-3'-nitro-2-biphenylsulphonamide (0.18 g), m.p. 114-115 C.; mass spectrum (+ve CI): 457 (M+H)+.
EXAMPLE 5 Preparation of 3-methoxy-5-methylpyrazin-2-amine 3-Methoxy-5-methyl-1-oxopyrazin-2-ylamine (1 g; 6.44 mmol) and methanol (50 ml) were charged initially together with 0.19 g of Pt/C-5 percent into an autoclave. The autoclave was first flushed with argon (three times), and a hydrogen pressure of 10 bar was then applied. The hydrogenation proceeded for 5 hours at 130 C. At 20 C., the autoclave was flushed with argon. The catalyst was filtered and washed with 5 ml of methanol. The solvent was completely removed by distillation. 0.85 g of 3-methoxy-5-methylpyrazin-2-amine was obtained. The yield of the product was 95 percent. Other data concerning the product was: 1 H NMR (DMSO-d6, 400 MHz)delta: 2.20 (s, 3H); 3.87 (s, 3H); 5.90 (s, 2H); 7.33 (s, 1H). Melting point: 75-76.5 C.
With sodium methylate; sodium; In methanol; water;
(i) 2-Amino-3-bromo-5-methylpyrazine (0.374 g) was added to a freshly prepared solution of sodium methoxide in methanol (made by addition of sodium (0.115 g) to methanol (6 ml)). The reaction was heated under reflux for 18 hours, cooled to ambient temperature and the solvent removed by evaporation. Water (5 ml) was added to the residue and extracted with dichloromethane (3*20 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by chromatography on silica gel, eluding with dichloromethane to give 2-amino-3-methoxy-5-methylpyrazine as a white crystalline solid (0.208 g, 75%), m.p. 67-69 C.; mass spectrum (+ve CI): 140 (M+H)+.
75%
With sodium methylate; sodium; In methanol; water;
(b) 2-Amino-3-bromo-5-methylpyrazine (0.374 g) was added to a freshly prepared solution of sodium methoxide in methanol (made by addition of sodium (0.115 g) to methanol (6 ml)). The reaction was heated under reflux for 18 hours, cooled to ambient temperature and the solvent removed by evaporation. Water (5 ml) was added to the residue and extracted with dichloromethane (3*20 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by chromatography on silica gel, eluding with dichloromethane to give 2-amino-3-methoxy-5-methylpyrazine as a white crystalline solid (0.208 g, 75%), m.p. 67-69 C.; mass spectrum (+ve CI): 140 (M+H)+.
75%
With sodium methylate; sodium; In methanol; water;
(ii) 2-Amino-3-bromo-5-methylpyrazine (0.374 g) was added to a freshly prepared solution of sodium methoxide in methanol (made by addition of sodium (0.115 g) to methanol (6 ml). The reaction mixture was heated under reflux for 18 hours, cooled to ambient temperature and the solvent removed by evaporation. Water (5 ml) was added to the residue and extracted with dichloromethane (3*20 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by chromatography on silica gel, eluding with dichloromethane to give 2-amino-3-methoxy-5-methylpyrazine as a white crystalline solid (0.208 g, 75%), m.p. 67-69 C.; mass spectrum (+ve CI): 140 (M+H)+.
3-methoxy-5-methylpyrazine-2-carboxamide[ No CAS ]
[ 89464-87-9 ]
Yield
Reaction Conditions
Operation in experiment
With potassium hydroxide; potassium hypobromite; bromine; In water;
(a) Synthesis of 3-methoxy-5-methylpyrazine-2-amine 3.71 g (56.2 mmol) of potassium hydroxide (85%) and 31 g of water were initially charged in a flask. At 1 C., 2.16 g (13.5 mmol) of bromine was added dropwise over a period of 10 minutes. This potassium hypobromite solution was added dropwise at 4 C. to an aqueous solution of 2.27 g (13.1 mmol) of 3-methoxy-5-methylpyrazine-2-carboxamide in 12 g of water. The mixture was stirred at 1 C. for one hour and then at 98 C. for 3 hours. The resultant 3-methoxy-5-methylpyrazine-2-amine was extracted at 20 C. using methylene chloride (2 times 25 ml).
With potassium hydroxide; potassium hypobromite; bromine; In water;
(b) Synthesis of 3-methoxy-5-methylpyrazine-2-amine 1.54 g (23.3 mmol) of potassium hydroxide (85%) and 15 g of water were initially charged in a flask. At 1 C., 1.08 g (5.53 mmol) of bromine was added dropwise over a period of 10 minutes. This potassium hypobromite solution was added dropwise at 4 C. to an aqueous solution of 1.04 g (5.76 mmol) of 3-methoxy-5-methylpyrazine-2-carboxamide in 6.5 g of water. The mixture was stirred at 1 C. for 1 hour and then at 83 C. for 3 hours. The 3-methoxy-5-methylpyrazine-2-amine was extracted at 20 C. using methylene chloride (2 times 15 ml).
N-(3-methoxy-5-methyl-2-pyrazinyl)-2-iodobenzenesulphonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In pyridine; water;
(iii) 2-IodobenzenesulphonyI chloride (obtained as described in J Org Chem, (1977), 42, 3265) (12.1 g) was added to a solution of <strong>[89464-87-9]2-amino-3-methoxy-5-methylpyrazine</strong> (5.6 g) in pyridine (100 ml) and the solution was heated at 70 C. for 8 hours. Volatile material was removed by evaporation and water (200 ml) was added to the residue. The mixture was extracted with ethyl acetate (2*200 ml) and the extracts were washed with 2M hydrochloric acid (200 ml) and water (200 ml). The extracts were dried (MgSO4) and the solvent was removed by evaporation. The residue was triturated with ether to give 2-iodo- N-(3-methoxy-5-methylpyrazin-2-yl)benzenesulphonamide (7.2 g), m.p. 136-138 C.; 1 H NMR (d6 -DMSO): 2.3 (s, 3H), 3.9 (s, 3H), 7.3(dt, 1H), 7.5-7.65 (m, 2H), 8.05-8.15 (m, 2H), 10.7-10.8 (br s, 1H).
With pyridine;dimethylaminopyridine; In water; at 60℃; for 24.0h;
StepO2: Synthesis of 3-Bromo- thiophene-2- sulfonic acid (3-methoxy-5-methyl-pyrazin-2-yl)-amide; To a stirred cold solution of <strong>[89464-87-9]3-methoxy-5-methyl-pyrazine-2-ylamine</strong> (2.5gm, 0.018mol) in pyridine (30ml) di-methyl amino pyridine (0.3gm, 0.002mol) was charged followed by 3- bromo-thiophene-2-sulfonyl chloride (6.5gm, 0.025mol). Reaction mixture was heated and stirred at 6O0C for 24 hrs. Pyridine was evaporated under vacuum. Crude was taken into ethyl acetate and washed with saturated sodium bicarbonate solution. Ethyl acetate layer was dried over sodium sulphate and concentrated under vacuum to give 4.4gm of 3- Bromo- thiophene-2- sulfonic acid (3-methoxy-5-methyl-pyrazin- 2-yl)-amide as a brown solid
[00791] To a mixture of <strong>[74290-65-6]3-bromo-5-methyl-pyrazin-2-amine</strong> (31 g, 164.87 mmol) in MeOH (150 mL) was added NaOMe (14 g, 263.79 mmol) in one portion at 30 C under N2. The mixture was stirred at 100 C for 6 hrs. The mixture was concentrated under reduced pressure and the resulting residue was dissolved in water (100 mL). The mixture was extracted with EtOAc and the combined organic layers were washed with brine (20 mL), dried with Na2S04, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (to afford 3-methoxy-5-methyl-pyrazin-2-amine (21 g, 92% yield) as a white solid. 1H MR (400 MHz, CDCh-d) delta ppm 7.39 (s, 1H) 4.59 (br s, 2 H) 3.97 (s, 3 H) 2.29 (s, 3 H)
With iodine; isopentyl nitrite; at 0 - 30℃; for 3.0h;
[00792] To a solution of <strong>[89464-87-9]3-methoxy-5-methyl-pyrazin-2-amine</strong> (21 g, 150.91 mmol) in CH2I2 (40 mL) was added isopentyl nitrite (35.36 g, 301.82 mmol, 40.64 mL) and I2 (45.96 g, 181.09 mmol, 36.48 mL) at 0 C. The mixture was warmed to 30 C and stirred at 30 C for 3 hrs. The reaction mixture was poured into 300 mL of saturated aq. Na2S03 and the aqueous phase was extracted with DCM. The combined organic layers were washed with brine, dried with anhydrous Na2S04, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography to afford 2-iodo-3-methoxy-5-methyl- pyrazine (21 g, 55.65% yield) as a yellow solid. NMR (400 MHz, CDCh-d) delta ppm 7.81 (s, 1H) 3.99 (s, 3 H) 2.40 (s, 3 H)
tert-butyl N-[(3S,4S)-8-[5-[(2-amino-3-chloro-4-pyridyl)sulfanyl]-6-methyl[1,2,4]triazolo[4,3-a]pyrazin-8-yl]-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl]carbamate[ No CAS ]
tert-butyl N-[(3S,4S)-8-[5-(2,3-dichlorophenyl)-6-methyl[1,2,4]triazolo[4,3-a]pyrazin-8-yl]-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl]carbamate[ No CAS ]
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
