Structure of Amino-3,5-dibromopyrazine
CAS No.: 24241-18-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Synonyms: 3,5-Dibromo-2-pyrazinamine; 3,5-Dibromopyrazin-2-ylamine
4.5
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CAS No. : | 24241-18-7 |
Formula : | C4H3Br2N3 |
M.W : | 252.89 |
SMILES Code : | NC1=NC=C(Br)N=C1Br |
Synonyms : |
3,5-Dibromo-2-pyrazinamine; 3,5-Dibromopyrazin-2-ylamine
|
MDL No. : | MFCD00673150 |
InChI Key : | DTLBKXRFWUERQN-UHFFFAOYSA-N |
Pubchem ID : | 620004 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335-H302+H312+H332 |
Precautionary Statements: | P261-P264-P270-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P330-P362-P403+P233-P501 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.84 |
TPSA ? Topological Polar Surface Area: Calculated from |
51.8 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.54 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.48 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.59 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.55 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.71 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.37 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.83 |
Solubility | 0.371 mg/ml ; 0.00147 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.17 |
Solubility | 1.69 mg/ml ; 0.00669 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.0 |
Solubility | 0.251 mg/ml ; 0.000993 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.79 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.46 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50.6% | at 20 - 110℃; | Step A: Preparation of ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylateTo a stirred solution of 2-amino-3,5-dibrompyrazine (20 g, 79mmol) in dimethylcarbonate (133 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 1 10 C for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over a2(S04) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6 percent) ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDCl3): δ =8.30 (s, 1 H), 8.27 (s, 1 H), 4.48 (q, 2H), 1 .43 (tr, 3H) ppm. |
50.6% | at 110℃; for 3 h; | Step A: Preparation of ethyl 6,8-dibromoimidazo[ 1 , 2-a]pyrazine-2-carboxylateTo a stirred solution of 2-amino-3, 5-dibrompyrazine (20 g, 79mmol) in dimethyicarbonate (1 33 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 1 10° C for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over Na2(S04) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6 percent) ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDC ): δ =8.30 (s, 1 H), 8.27 (s, 1 H), 4.48 (q, 2H), 1 .43 (tr, 3H) ppm. |
50.6% | at 20 - 110℃; for 3 h; | Intermediate Example 1 -2: Preparation of (6,8-dibromoimidazo[1 ,2-a]pyrazin-2- yl)methanolStep A: Preparation of ethyl 6,8-dibromoimidazo[1 , 2-a]pyrazi'ne-2-carboxylateTo a stirred solution of 2-amino-3,5-dibrompyrazine (20 g, 79mmol) in dimethylcarbonate (133 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 1 10° C for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over a2(S04) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6 percent) ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDCI3): δ =8.30 (s, 1 H), 8.27 (s, 1 H), 4.48 (q, 2H), 1 .43 (tr, 3H) ppm. |
50.6% | at 110℃; | Step A: Preparation of ethyl 6,8-dibromoimidazo[1,2-a]pyrazine-2-carboxylateTo a stirred solution of 2-amino-3,5-di brom pyrazi ne (20 g, 79m mol ) i n dimethylcarbonate (133 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 1 10° C for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over Na2(S04) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6 3/4) ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDCl3): δ =8.30 (s, 1 H), 8.27 (s, 1 H), 4.48 (q, 2H), 1 .43 (tr, 3H) ppm. |
50.6% | at 20 - 110℃; | To a stirred solution of 2-amino-3,5-dibrompyrazine (20 g, 79 mmol) in dimethylcarbonate (133 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 110° C. for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over Na2(SO4) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6percent) ethyl 6,8-dibromoimidazo[1,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, |
50.6% | at 110℃; for 3 h; | To a stirred solution of 2-amino-3,5-dibrompyrazine (20 g, 79 mmol) in dimethylcarbonate (133 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 110° C. for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over Na2(SO4) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6percent) ethyl 6,8-dibromoimidazo[1,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDCl3: δ=8.30 (s, 1H), 8.27 (s, 1H), 4.48 (q, 2H), 1.43 (tr, 3H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.7% | at 10 - 20℃; for 1.5 h; | Step 3: 2-bromo-7-nitro-5H-pyrrolo[2,3-b]pyrazine[00199] 2-bromo-5H-pyrrolo[2,3-b]pyrazine (20 g, 101.0 mmol) was dissolved in ice-cold sulfuric acid (140.0 mL) , producing a bright orange solution, and concentrated nitric acid (12.73 g, 8.470 mL, 202.0 mmol) was added drop wise with stirring over 30 min keeping the temperature under 10 °C (turning the solution to a clear red colour). The reaction was removed from the ice bath after 30 min and allowed to warm to ambient temperature and left to stir at ambient temperature for 1 hour. The reaction mixture was poured onto ice to obtain a yellow solid. The solid was filtered, washed with water to give 2-bromo-7-nitro-5H- pyrrolo[2,3-b]pyrazine the desired product as a yellow solid. (21.76 g, 88.7percent). MS (ES+) 244.87. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine; at 130℃; for 5.0h;Microwave irradiation; | Example 52 (£)-2-(1 -(1 -(Quinolin-6-ylmethyl)-1 H-[1 ,2,3]triazolo[4,5-b]pyrazin-6-yl)ethylidene)hydrazinecarboxamide6-Bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamine (52.1 )A mixture of <strong>[99071-54-2]quinolin-6-ylmethanamine</strong> (3.6g, 22.76mmol), 3,5-dibromopyrazin-2-amine (5.75 g, 22.76 mmol) and triethyl amine (4.61 g, 45.5 mmol) was heated in a microwave to130 0C for 5h. The reaction mixture was diluted with CH2CI2 and water and the organic layer was separated, washed with aqueous NH4CI, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography with EA:Hexanes to provide 6- bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamine (6.93 g, 92%). LCMS (method A): [MH]+ = 330, tR = 4.89 min. |
92% | With triethylamine; at 130℃; for 5.0h;Microwave irradiation; | A mixture of <strong>[99071-54-2]quinolin-6-ylmethanamine</strong> (3.6g, 22.76mmol), 3,5-dibromopyrazin-2-amine (5.75 g, 22.76 mmol) and triethyl amine (4.61 g, 45.5 mmol) was heated with microwave irradiation at 130 0C for 5 h. The reaction mixture was diluted with CH2CI2 and water and the organic layer was separated, washed with aqueous NH4CI, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography withEtOAc:hexanes to provide 6.93 g (92%) of the title compound. LCMS (method A): [MH]+ = 330, tR = 4.89 min. |
59% | With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 180℃; for 12.0h;Sealed tube; | 2-Amino-3,5-dibromopyrazine (a, 6.1 g, 24.1 mmol),<strong>[99071-54-2]quinolin-6-ylmethanamine</strong> (b1, 3.8 g,24.1 mmol) and DIPEA (8.6 ml, 52.1 mmol) were dissolved in NMP (20 ml), thenthe mixture was stirred overnight at 180C in a sealed tube. After removal ofsolvents, the residue was purified by flash column chromatography to afford6-bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamineas a yellow solid (c1, 4.7 g, 59%yield). LC-MS (ESI): [M+H]+=330. 1H NMR (400 MHz, DMSO-d6) delta 8.85 (dd, J1=4.4Hz, J2=1.6 Hz, 1H), 8.33(d, J=8.4 Hz, 1H), 7.99 (d, J=8.8 Hz, 1H)7.87(s, 1H), 7.73 (dd, J1=8.8Hz, J2=2.0 Hz, 1H), 7.50(dd, J1=8.4 Hz, J2=4.4 Hz, 1H), 7.21 (s, 1H),7.16 (t, J=5.6 Hz, 1H), 6.25 (s, 2H), 4.69 (d, J=5.6 Hz, 2H). |
59% | With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 130℃;Inert atmosphere; | 3,5-Dibromopyrazin-2-amine (6.1 g, 24 mmol), 6-quinolinemethyleneamine (3.8 g, 24 mmol) And N,N-diisopropylethylamine (DIPEA) (8.6 mL, 48 mmol) were added to NMP (20 mL) The reaction was carried out overnight at 130 C under argon. The reaction mixture was evaporated to remove DIPEA. The residue was poured into water (100 mL) and extracted with dichloromethane (30 mL x 3). The organic phase was washed with water and washed with brine. After drying, flash column chromatography gave 4.7 g of tan product. Yield: 59%. |
49% | With N-ethyl-N,N-diisopropylamine; at 130℃; for 5.0h; | Method 3 6-bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamine: A mixture of <strong>[99071-54-2]quinolin-6-ylmethanamine</strong> (13 g, 82 mmol), 3,5-dibromopyrazin-2-amine (21 g, 82 mmol) and di-isopropylethylamine (16 mL, 89 mmol) was heated to 130 C. for five hours. The reaction was diluted with dichloromethane:ethanol (9:1) and the resulting suspension was filtered. The precipitate was washed sequentially with water and ether and air dried to afford 6-bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamine (13 g, 49%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 150℃; for 13h;Microwave irradiation; | PREPARATION 81 5-Bromo-3-(tetrahydro-2H-pyran-4-yl)-1-[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyrazin-2-one [Show Image]a) 5-Bromo-N3-(tetrahydro-2H-pyran-4-yl)pyrazine-2,3-diamine A mixture of 3,5-dibromopyrazin-2-amine (0.400 g, 1.6 mmol), <strong>[33024-60-1]tetrahydro-2H-pyran-4-amine hydrochloride</strong> (0.441 g, 3.20 mmol) and N,N-diisopropylethylamine (0.83 mL, 4.8 mmol) in n-butanol (3 mL) was stirred and heated under microwave irradiation ("Initiator sixty" from Biotage.(R).) at 150 °C. After 13 hours, the mixture was cooled and the mixture was partitioned between ethyl acetate and water. The organic layer was dried (MgSO4) and concentrated and the residue was purified by flash chromatography (2:1 hexanes/ethyl acetate) to give the title compound (0.34 g, 78percent) as a white solid. LRMS (m/z): 273, 275 (M+1)+.1H NMR (300 MHz, CDCl3) delta ppm 1.54 (dd, 2H), 1.97 - 2.18 (m, 2H), 3.57 (t, 2H), 3.93 - 4.21 (m, 5H), 7.26 - 7.28 (m, 1H), 7.47 (s, 1H). |
78% | With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 150℃; for 13h;Microwave irradiation; | PREPARATION 81 5-Bromo-3-(tetrahydro-2H-pyran-4-yl)-1-[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyrazin-2-one a) 5-Bromo-N3-(tetrahydro-2H-pyran-4-yl)pyrazine-2,3-diamine A mixture of 3,5-dibromopyrazin-2-amine (0.400 g, 1.6 mmol), <strong>[33024-60-1]tetrahydro-2H-pyran-4-amine hydrochloride</strong> (0.441 g, 3.20 mmol) and N,N-diisopropylethylamine (0.83 mL, 4.8 mmol) in n-butanol (3 mL) was stirred and heated under microwave irradiation ("Initiator sixty" from Biotage.(R).) at 150 °C. After 13 hours, the mixture was cooled and the mixture was partitioned between ethyl acetate and water. The organic layer was dried (MgSO4) and concentrated and the residue was purified by flash chromatography (2:1 hexanes/ethyl acetate) to give the title compound (0.34 g, 78percent) as a white solid. LRMS (m/z): 273, 275 (M+1)+.1H NMR (300 MHz, CDCl3) delta ppm 1.54 (dd, 2H), 1.97 - 2.18 (m, 2H), 3.57 (t, 2H), 3.93 - 4.21 (m, 5H), 7.26 - 7.28 (m, 1H), 7.47 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50.6% | In carbonic acid dimethyl ester; at 20 - 110℃; | Step A: Preparation of ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylateTo a stirred solution of 2-amino-3,5-dibrompyrazine (20 g, 79mmol) in dimethylcarbonate (133 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 1 10 C for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over a2(S04) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6 %) ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDCl3): delta =8.30 (s, 1 H), 8.27 (s, 1 H), 4.48 (q, 2H), 1 .43 (tr, 3H) ppm. |
50.6% | In carbonic acid dimethyl ester; at 110℃; for 3.0h; | Step A: Preparation of ethyl 6,8-dibromoimidazo[ 1 , 2-a]pyrazine-2-carboxylateTo a stirred solution of 2-amino-3, 5-dibrompyrazine (20 g, 79mmol) in dimethyicarbonate (1 33 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 1 10 C for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over Na2(S04) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6 %) ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDC ): delta =8.30 (s, 1 H), 8.27 (s, 1 H), 4.48 (q, 2H), 1 .43 (tr, 3H) ppm. |
50.6% | In carbonic acid dimethyl ester; at 20 - 110℃; for 3.0h; | Intermediate Example 1 -2: Preparation of (6,8-dibromoimidazo[1 ,2-a]pyrazin-2- yl)methanolStep A: Preparation of ethyl 6,8-dibromoimidazo[1 , 2-a]pyrazi'ne-2-carboxylateTo a stirred solution of 2-amino-3,5-dibrompyrazine (20 g, 79mmol) in dimethylcarbonate (133 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 1 10 C for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over a2(S04) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6 %) ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDCI3): delta =8.30 (s, 1 H), 8.27 (s, 1 H), 4.48 (q, 2H), 1 .43 (tr, 3H) ppm. |
50.6% | In carbonic acid dimethyl ester; at 110℃; | Step A: Preparation of ethyl 6,8-dibromoimidazo[1,2-a]pyrazine-2-carboxylateTo a stirred solution of 2-amino-3,5-di brom pyrazi ne (20 g, 79m mol ) i n dimethylcarbonate (133 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 1 10 C for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over Na2(S04) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6 ¾) ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDCl3): delta =8.30 (s, 1 H), 8.27 (s, 1 H), 4.48 (q, 2H), 1 .43 (tr, 3H) ppm. |
50.6% | at 20 - 110℃; | To a stirred solution of 2-amino-3,5-dibrompyrazine (20 g, 79 mmol) in dimethylcarbonate (133 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 110 C. for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over Na2(SO4) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6%) ethyl 6,8-dibromoimidazo[1,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, |
50.6% | In water; at 110℃; for 3.0h; | To a stirred solution of 2-amino-3,5-dibrompyrazine (20 g, 79 mmol) in dimethylcarbonate (133 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 110 C. for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over Na2(SO4) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6%) ethyl 6,8-dibromoimidazo[1,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDCl3: delta=8.30 (s, 1H), 8.27 (s, 1H), 4.48 (q, 2H), 1.43 (tr, 3H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | With bis-triphenylphosphine-palladium(II) chloride; triethylamine; In tetrahydrofuran; at 60℃; for 3h;Inert atmosphere; | General procedure: Triethylamine (2.76 mL, 19.77 mmol) was added to 3,5-dibromopyrazin-2-amine (0.5 g, 1.98 mmol), arylacetylene (1.98 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.056 g, 0.08 mmol) in degassed THF (10 mL) under nitrogen. The resulting mixture wasstirred at 60 C for 3 hours. The reaction mixture was then evaporated to dryness and the crude product was purified by flash silica chromatography. Pure fractions were combined and evaporated to dryness to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | With triethylamine; In dimethyl sulfoxide; at 130℃; | [0310] Tert-Butyl 3- (aminomethyl) piperidine-1-carboxylate (4.97 g, 22.40 mmol) was dissolved in DMSO (80 ml) 3,5-dibromopyrazine-2-amine (8.5 g, 33.60 mmol) and Et3N (6.3 ml) were added and the mixture was stirred overnight at 130 deg. After completion of the reaction, the reaction mixture was extracted with H2O, EA and brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by column chromatography (EA : Hex = 1: 1) to give tert-butyl 3 - (((3-amino-6-bromopyran- 2- yl) amino) methyl) piperidine- The rate (2.19 g, two steps: 26percent) was obtained. |
2.19 g | With triethylamine; In dimethyl sulfoxide; at 130℃; | tert-butyl3-(((3-amino-6-bromopyrazin-2-yl)amino)methyl)piperidine-1-carboxylate <strong>[162167-97-7]tert-butyl 3-(aminomethyl)piperidine-1-carboxylate</strong> (4.97 g, 22.40 mmol) was dissolved in DMSO (80 ml), and then 3,5-dibromopyrazine-2-amine (8.5 g, 33.60 mmol) and Et3N (6.3 ml) were added, followed by stirring at 130° C. overnight. After the completion of the reaction, the reaction mixture was extracted with H2O, EA, and brine, followed by drying (Na2SO4), filtration, and concentration under reduced pressure, and the residue was purified by column chromatography (EA:Hex=1:1), to give tert-butyl 3-(((3-amino-6-bromopyrazine-2-yl)amino)methyl)piperidine-1-carboxylate (2.19 g, two steps: 26percent). 1H-NMR (300 MHz, CDCl3) delta 7.39 (s, 1H), 4.64-4.23 (m, 2H), 3.79-2.92 (m, 5H), 2.25-1.19 (m, 4H), 1.46 (s, 9H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | With triethylamine; In dimethyl sulfoxide; at 130℃; | [0371] (R) -tert-butyl 3- (aminomethyl) piperidine-1-carboxylate (4.97 g, 22.40 mmol) was dissolved in DMSO (80 ml), and 3,5-dibromopyrazine-2-amine (8.5 g, 33.60 mmol) and Et3N (6.3 ml), and the mixture was stirred overnight at 130 deg. After completion of the reaction, the reaction mixture was extracted with H2O, EA and brine, dried (Na2SO4) Filtered, concentrated under reduced pressure, The residue was purified by tube chromatography (EA: Hex = 1: 1) (R) -tert- butyl 3 - (((3-Amino-6-bromopyrazine-2-yl) amino) methyl) piperidine-1-carboxylate (2.19 g, two steps: 26%) was obtained. |
2.19 g | With triethylamine; In dimethyl sulfoxide; at 130℃; | (R)-tert-butyl 3-(((3-amino-6-bromopyrazine-2-yl)amino)methyl)piperidine- 1 -carboxylate._10239] (R)-tert-butyl 3-(aminomethyl)piperidine-1 -carboxylate (4.97 g, 22.40 mmol) was dissolved in DMSO (80 ml), and then 3,5-dibromopyrazine-2-amine (8.5 g, 33.60 mmol) and Et3N (6.3 ml) were added, followed by stirring at 130 C. overnight. Afier the completion of the reaction, the reaction mixture was extracted with H20, EA, and brine, followed by drying (Na2SO4), filtration, and concentration under reduced pressure, and the residue was purified by column chromatography (EA:Hex=1:1), to give (R)-tert-butyl 3-(((3-amino-6-bromopyrazine-2-yl)amino)methyl)piperi- dine-i-carboxylate (2.19 g, two steps: 26%).10240] ?H-NMR (300 MHz, CDC13) oe 7.39 (s, 1H), 4.64-4.23 (m, 2H), 3.79-2.92 (m, 5H), 2.25-1.19 (m, 4H), 1.46 (s, 9H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | (R) -3- (3- amino-6-bromo-pyrazin-2-yloxy) pyrrolidine-1-carboxylic acid tert-butyl ester: 0.105 g of sodium hydride / mineral oil (2.62 mmol) with n-hexane washed twice, and pooled into 2.0 ml of tetrahydrofuran, was added 0.350 g (R) -1- tert-butoxycarbonyl-3-hydroxypyrrolidine (1.87 mmol), the reaction mixture was stirred at room temperature for 5 minutes, the gelable reaction, followed by addition of 2.0 ml containing 0.235 g of 2-amino-3,5-dibromo-pyrazine (1.87 mmol) in tetrahydrofuran, the reaction mixture was heated to 50 deg.] C for 2.5 hours, the reaction mixture was cooled to and saturated sodium bicarbonate was added at room temperature, the whole solution was diluted with ethyl acetate and washing with saturated sodium chloride, dried over sodium sulfate, filtered and concentrated in vacuo, the crude product with 0-70% ethyl acetate in hexane as solvent red extract was purified by flash column isolated 160 mg (48% yield) of product. (Rf = 0.48 in 1: 1 hexane / ethyl acetate). |
Tags: 24241-18-7 synthesis path| 24241-18-7 SDS| 24241-18-7 COA| 24241-18-7 purity| 24241-18-7 application| 24241-18-7 NMR| 24241-18-7 COA| 24241-18-7 structure
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