Structure of 1303968-25-3
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CAS No. : | 1303968-25-3 |
Formula : | C5H5BrN4O2 |
M.W : | 233.02 |
SMILES Code : | O=C(C1=NC(Br)=C(N)N=C1N)O |
MDL No. : | MFCD18914368 |
InChI Key : | FDPDGMKZZNURGR-UHFFFAOYSA-N |
Pubchem ID : | 53407675 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
With water; sodium hydroxide; In methanol; for 3.0h;Reflux; | General procedure: A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60C. Yield: 99.6 g (107% of theory) C5H5ClN4O2 ESI Mass spectrum: m/z = 189 [M+H]+; m/z = 187 [M-H]- | |
With water; sodium hydroxide; In methanol; for 3.0h;Reflux; | General procedure: 3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60 C. Yield: 99.6 g (107% of theory) C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]- | |
With water; sodium hydroxide; In methanol; for 3.0h;Reflux; | General procedure: A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 I) and NaOH (6 mol/l in water; 240 mL; 1 .44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60C. Yield: 99.6 g (107% of theory). C5H5ClN4O2. ESI Mass spectrum: m/z = 189 [M+H]+; m/z = 187 [M-H]-. |
With water; sodium hydroxide; In methanol; for 3.0h;Reflux; | General procedure: Intermediate 1: 3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 L) and NaOH (6 mol/L in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to room temperature and then neutralised by addition of hydrochloric acid (6 M in water; ca. 120 mL). Water (200 mL) is added. The precipitate formed is collected by filtration while applying suction, washed with water and dried at 60 C. Yield: 99.6 g (107% of theory). ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]- | |
With sodium hydroxide; In methanol; water; for 3.0h;Reflux; | General procedure: A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60 C. C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]- | |
General procedure: Intermediate A.1 3,5-diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 I) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60C. C5H5CIN4O2 ESI Mass spectrum: m/z = 189 [M+H]+; m/z = 187 [M-H]" | ||
With water; sodium hydroxide; In methanol; for 3.0h;Reflux; | General procedure: A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60 C. C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]- | |
With water; sodium hydroxide; In methanol; for 3.0h;Reflux; | General procedure: 3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 ml; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60 C. C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]- | |
With sodium hydroxide; In methanol; water; for 3.0h;Reflux; | General procedure: 3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 ml; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60 C. C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]- | |
With sodium hydroxide; In methanol; water; for 3.0h;Reflux; | General procedure: 3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 ml; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60 C. C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]- | |
With sodium hydroxide; In methanol; water; for 3.0h;Reflux; | General procedure: Intermediate A.13,5-Diamino-6-chloropyrazine-2-carboxylic acidA mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 I) and NaOH (6 mol/l in water; 240 ml; 1 .44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 ml_). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60C.C5H5CIN402 ESI Mass spectrum: m/z = 189 [M+H]+; m/z = 187 [M-H]- | |
With sodium hydroxide; In methanol; water; for 3.0h;Reflux; | General procedure: Intermediate A.13,5-Diamino-6-chloropyrazine-2-carboxylic acidA mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 ml; 1 .44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 ml_). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60C. | |
General procedure: Intermediate A. l : 3,5-Diamino-6-chloropyrazine-2-carboxylic acidA mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 1) and NaOH (6 mol/1 in water; 240 ml; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/1 in water; approx. 240 riiL). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60C.C5H5CIN4O2ESI Mass spectrum: m z = 189 [M+H]+; m z = 187 [M-H]~ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage 1 : A mixture of 2-methyl-2-butanol (5.75 mL; 51 mmol) and 5-methylisoxazole (4.42 mL; 51 mmol) is cooled with an ice-bath. Trifluoromethanesulphonic acid (4.84 mL; 54 mmol) is added dropwise with continued cooling. The resulting mixture is stirred over night without further cooling. Stage 2: To a solution or suspension of <strong>[1303968-25-3]3,5-diamino-6-bromopyrazine-2-carboxylic acid</strong> (Intermediate A.62; 5.00 g; 21 .5 mmol) and triethylamine (7.48 mL; 54 mmol) in DMF (50 mL) cooled with an ice-bath is added dropwise the mixture prepared in stage 1 . The resulting mixture is stirred for 4 h at r.t., then poured on ice-water. The precipitate formed is filtered off with suction, washed with water and dried at 50C to yield the title compound. Yield: 7.53 g (91 % of theory) C14H20BrN5O5 ESI Mass spectrum: m/z = 386 [M+H]+; m/z = 384 [M-H]" |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage 1: A mixture of 2-methyl-2-butanol (5.75 mL; 51 mmol) and 5-methylisoxazole (4.42 mL; 51 mmol) is cooled with an ice-bath. Trifluoromethanesulphonic acid (4.84 mL; 54 mmol) is added drop- wise with continued cooling. The resulting mixture is stirred over night without further cooling. Stage 2: To a solution or suspension of <strong>[1303968-25-3]3,5-diamino-6-bromopyrazine-2-carboxylic acid</strong> (Intermediate A.2; 5.00 g; 21.5 mmol) and triethylamine (7.48 mL; 54 mmol) in DMF (50 mL) cooled with an ice-bath is added dropwise the mixture prepared in stage 1. The resulting mixture is stirred for 4 h at r.t., then poured on ice-water. The precipitate formed is filtered off with suction, washed with water and dried at 50C to yield the title compound. Yield: 7.53 g (91 % of theory). C14H20BrN5O3. ESI Mass spectrum: m/z = 386 [M+H]+; m/z = 384 [M-H]-. | |
7.53 g | Intermediate B.62 RRN No.30 1-(2-Methyl-2-butyl-carbamoyl)prop-1-en-2-yl 3,5-diamino-6-bromopyrazine-2-carboxylate Stage 1: [0313] A mixture of 2-methyl-2-butanol (5.75 mL; 51 mmol) and 5-methylisoxazole (4.42 mL; 51 mmol) is cooled with an ice-bath. Trifluoromethanesulfonic acid (4.84 mL; 54 mmol) is added dropwise with continued cooling. The resulting mixture is stirred over night without further cooling. Stage 2: [0314] To a solution or suspension of <strong>[1303968-25-3]3,5-diamino-6-bromopyrazine-2-carboxylic acid</strong> (Intermediate A.62; 5.00 g; 21.5 mmol) and triethylamine (7.48 mL; 54 mmol) in DMF (50 mL) cooled with an ice-bath is added dropwise the mixture prepared in stage 1. The resulting mixture is stirred for 4 h at r.t., then poured on ice-water. The precipitate formed is filtered off with suction, washed with water and dried at 50 C. to yield the title compound. [0315] Yield: 7.53 g (91% of theory) [0316] C14H20BrN5O3 ESI Mass spectrum: m/z=386 [M+H]+; m/z=384 [M-H]- | |
Intermediate B.2 RRN 185 1-(2-methyl-2-butyl-carbamoyl)prop-1-en-2-yl 3,5-diamino-6-bromopyrazine-2-carboxylate [0469] 2-methyl-2-butanol (5.75 mL; 51 mmol) and 5-methylisoxazole (4.42 mL; 51 mmol) is cooled with an ice-bath. Trifluoromethanesulphonic acid (4.84 mL; 54 mmol) is added dropwise with continued cooling. The resulting mixture is stirred over night without further cooling. Stage 2: [0471] To a solution or suspension of <strong>[1303968-25-3]3,5-diamino-6-bromopyrazine-2-carboxylic acid</strong> (Intermediate A.2; 5.00 g; 21.5 mmol) and triethylamine (7.48 mL; 54 mmol) in DMF (50 mL) cooled with an ice-bath is added dropwise the mixture prepared in stage 1. The resulting mixture is stirred for 4 h at r.t., then poured on ice-water. The precipitate formed is filtered off with suction, washed with is water and dried at 50 C. to yield the title compound. [0472] Yield: 7.53 g (91% of theory) [0473] C14H20BrN5O3 ESI Mass spectrum: m/z=386 [M+H]+; m/z=384 [M-H]- |
7.53 g | Intermediate 2.1 1-(2-Methyl-2-butyl-carbamoyl)prop-1-en-2-yl 3,5-diamino-6-bromopyrazine-2 Stage 1: A mixture of 2-methyl-2-butanol (5.75 mL; 51 mmol) and 5-methylisoxazole (4.42 mL; 51 mmol) is cooled with an ice-bath. Trifluoromethanesulphonic acid (4.84 mL; 54 mmol) is added dropwise with continued cooling. The resulting mixture is stirred overnight without further cooling. Stage 2: To a solution or suspension of <strong>[1303968-25-3]3,5-diamino-6-bromopyrazine-2-carboxylic acid</strong> (Intermediate 1.1; 5.00 g; 21.5 mmol) and triethylamine (7.48 mL; 54 mmol) in DMF (50 mL) cooled with an ice-bath is added dropwise the mixture prepared in stage 1. The resulting mixture is stirred for 4 h at r.t., then poured on ice-water. The precipitate formed is filtered off with suction, washed with water and dried at 50 C. to yield the title compound. Yield: 7.53 g (91% of theory) C14H20BrN5O3 ESI Mass spectrum: m/z=386 [M+H]+; m/z=384 [M-H]- | |
Intermediate B.2 1 -(2-Methyl-2-butyl-carbamoyl)prop-1 -en-2-yl 3,5-diamino-6-bromopyrazine-2-carboxylate Stage 1 : A mixture of 2-methyl-2-butanol (5.75 mL; 51 mmol) and 5-methylisoxazole (4.42 mL; 51 mmol) is cooled with an ice-bath. Trifluoromethanesulphonic acid (4.84 mL; 54 mmol) is added drop- wise with continued cooling. The resulting mixture is stirred over night without further cooling. Stage 2: To a solution or suspension of <strong>[1303968-25-3]3,5-diamino-6-bromopyrazine-2-carboxylic acid</strong> (Intermediate A.2; 5.00 g; 21.5 mmol) and triethylamine (7.48 mL; 54 mmol) in DMF (50 mL) cooled with an ice-bath is added dropwise the mixture prepared in stage 1. The resulting mixture is stirred for 4 h at r.t., then poured on ice-water. The precipitate formed is filtered off with suction, washed with water and dried at 50C to yield the title compound. Ci4H2oBrN503 ESI Mass spectrum: m/z = 386 [M+H]+; m/z = 384 [M-H]" | ||
is Stage 1: [0161] A mixture of 2-methyl-2-butanol (5.75 mL; 51 mmol) and 5-methylisoxazole (4.42 mL; 51 mmol) is cooled with an ice-bath. Trifluoromethanesulphonic acid (4.84 mL; 54 mmol) is added dropwise with continued cooling. The resulting mixture is stirred over night without further cooling. Stage 2: [0162] To a solution or suspension of <strong>[1303968-25-3]3,5-diamino-6-bromopyrazine-2-carboxylic acid</strong> (Intermediate A.2; 5.00 g; 21.5 mmol) and triethylamine (7.48 mL; 54 mmol) in DMF (50 mL) cooled with an ice-bath is added dropwise the mixture prepared in stage 1. The resulting mixture is stirred for 4 h at r.t., then poured on ice-water. The precipitate formed is filtered off with suction, washed with water and dried at 50 C. to yield the title compound. [0163] C14H20BrN5O3 ESI Mass spectrum: m/z=386 [M+H]+; m/z=384 [M-H]- | ||
Stage 1:A mixture of 2-methyl-2-butanol (5.75 mL; 51 mmol) and 5-methylisoxazole (4.42 mL; 51 mmol) is cooled with an ice-bath. Trifluoromethanesulphonic acid (4.84 mL; 54 mmol) is added dropwise with continued cooling. The resulting mixture is stirred over night without further cooling.Stage 2:To a solution or suspension of <strong>[1303968-25-3]3,5-diamino-6-bromopyrazine-2-carboxylic acid</strong> (Intermediate A.2; 5.00 g; 21.5 mmol) and triethylamine (7.48 mL; 54 mmol) in DMF (50 mL) cooled with an ice-bath is added dropwise the mixture prepared in stage 1. The resulting mixture is stirred for 4 h at r.t., then poured on ice-water. The precipitate formed is filteredoff with suction, washed with water and dried at 50C to yield the title compound. C14H20BrN5O3 ESI Mass spectrum: mlz = 386 [M+H]+; mlz = 384 [M-Hf |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In N,N-dimethyl-formamide; at 20.0℃; for 4.0h; | To a solution or suspension of 3,5-diamino-6-chloropyrazine-2-carboxylic acid (intermediate A.1; 14.0 g; 74.2 mmol) and triethylamine (31.0 mL; 222 mmol) in DMF (100 mL) is added the mixture prepared in stage 1. The resulting mixture is stirred for 4 h at r.t. Ice-water is added with stirring. The precipitate formed is filtered off with suction, washed with water and dried at 65 C. to yield the title compound. [0278] C13H18ClN5O3 ESI Mass spectrum: m/z=328 [M+H]+; m/z=326 [M-H]- [0279] TLC (Silica; DCM/MeOH 9:1): Rf=0.4 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In N,N-dimethyl-formamide; at 20.0℃; for 4.0h; | To a solution or suspension of <strong>[1303968-25-3]3,5-diamino-6-bromopyrazine-2-carboxylic acid</strong> (Intermediate A.2; 5.00 g; 21.5 mmol) and triethylamine (7.48 mL; 54 mmol) in DMF (50 mL) cooled with an ice-bath is added dropwise the mixture prepared in stage 1. The resulting mixture is stirred for 4 h at r.t., then poured on ice-water. The precipitate formed is filtered off with suction, washed with water and dried at 50 C. to yield the title compound. [0283] C14H20BrN5O3 ESI Mass spectrum: m/z=386 [M+H]+; m/z=384 [M-H]- |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20.0℃; | General procedure: A mixture of 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid (Intermediate A.1; 10 mg; 0.053 mmol), the amine intermediate XIV.1 (as a TFA salt; 22 mg; 0.042 mmol) the coupling reagent HATU (50 mg; 0.132 mmol) and DIPEA (100 μl; 0.59 mmol) in DMF (5 ml) is stirred at r.t. over night. The mixture is purified by RP-HPLC (column: SunFire C18; water-ACN; modifier TFA) to yield the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
mixture of 3,5-diamino-6-bromo-pyrazine-2-carboxylic acid (Intermediate A.2; 60 mg; 0.25 mmol), the amine intermediate X.3 (as a iodide salt; 0.14 g; 0.30 mmol) the coupling reagent HATU (0.10 g; 0.25 mmol) and TEA (70 μl; 0.50 mmol) in DMF (2 ml) is stirred at r.t. over night. The mixture is purified by RP-HPLC (column: SunFire C18; water-ACN; modifier TFA) to yield the title compound. C22H31BrN7O5×2TFA ESI Mass spectrum: m/z=552 [M]+; HPLC analytics: RT=0.99 min (HPLC method 4) | ||
Example 2.1A mixture of 3,5-diamino-6-bromo-pyrazine-2-carboxylic acid (Intermediate A.2; 60 mg; 0.25 mmol), the amine intermediate X.3 (as a iodide salt; 0.14 g; 0.30 mmol) the coupling reagent HATU (0.10 g; 0.25 mmol) and TEA (70 μΙ; 0.50 mmol) in DMF (2 ml) is stirred at r.t. over night. The mixture is purified by RP-HPLC (column: SunFire C18; water-ACN; modifier TFA) to yield the title compound. C22H31BrN7O5 x2TFA ESI Mass spectrum: m/z = 552 [M]+ HPLC analytics: RT = 0.99 min (HPLC method 4) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In dichloromethane; at 20.0℃; for 2.0h; | 10645] To (S)-tert-butyl (3-(2-(1 -aminoethyl)-5-chioro-4- oxoquinazolin-3(4R)-yl)propyl)carbamate and 3,5-diamino- 6-bromopyrazine-2-carboxylic acid in DCM was added RATU and DIEA. The reaction was allowed to stir at RT for 2 hours. The reaction was monitored by LCMS. Upon completion the reaction was concentrated to dryness and purified by silica gel chromatography (20-80% EtOAc/hexanes) to give (S)-tert-butyl (3-(5-chloro-2-(1 -(3,5-diamino-6- bromopyrazine-2-carboxamido)ethyl)-4-oxoquinazolin-3(4R)-yl)propyl)carbamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20.0℃; for 2.0h; | General procedure: A mixture of the carboxylic acid intermediate IV.2 (2.00 g; 4.24 mmol), the amine (R,R)-3,4- dihydroxypyrrolidine (0.592 g; 4.24 mmol), TBTU (1.36 g; 4.24 mmol), triethylamine (1.79 ml; 12.7 mmol) and DMF (10 ml) ist stirred at r.t. for 2h. The mixture is poured on ice-water and extracted with EE. The organic layer is separated, dried (MgS04), filtered and evaporated. The residue is purified by silica gel chromatography (DCM / MeOH 0->10 ).C27H28N4O7 ESI Mass spectrum: m/z = 521 [M+H]+ |