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CAS No. : | 39889-94-6 | MDL No. : | MFCD09608109 |
Formula : | C5H7N3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | VGPRNGGSKJHOFE-UHFFFAOYSA-N |
M.W : | 109.13 | Pubchem ID : | 295764 |
Synonyms : |
|
Num. heavy atoms : | 8 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.2 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 31.4 |
TPSA : | 51.8 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -7.02 cm/s |
Log Po/w (iLOGP) : | 1.05 |
Log Po/w (XLOGP3) : | -0.08 |
Log Po/w (WLOGP) : | 0.38 |
Log Po/w (MLOGP) : | -0.72 |
Log Po/w (SILICOS-IT) : | 0.69 |
Consensus Log Po/w : | 0.26 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.02 |
Solubility : | 10.4 mg/ml ; 0.0952 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.56 |
Solubility : | 30.3 mg/ml ; 0.278 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.62 |
Solubility : | 2.64 mg/ml ; 0.0242 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.26 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
79% | With palladium 10% on activated carbon; hydrogen; sodium hydroxide In diethyl ether; water at 20℃; for 22 h; | Example 77 (1 S,2R)-2-(4-(diisobutylamino)-3-(3-(2-methylpyrimidin-5-yl)ureido)phenyl)cyclopropanecarboxylic acid 77A. 2-methylpyrimidine-5-amineA solution of 4,6-dichloro-2-methylpyrimidin-5-amine (2 g, 11.23 mmol) in ethylether (93 ml) was treated with sodium hydroxide (7.37 g, 184 mmol) in water (22.05 ml)and 10percent palladium on carbon (0.161 g, 1.5 17 mmol). The mixture was shaken at rt on aParr shaker under 50 psi of H2 gas for 22 h. The reaction was filtered through Celite andthe filter cake was washed with DCM. The solvent from the filtrate was evaporated togive a yellow residue. The suspension was re-dissolved in DCM and water. The aqueous layer was neutralized to approximately pH 6 with 4N HC1, then extracted with DCM (3X). The combined organic phases were dried over anhydrous Na2SO4, filtered, and concentrated to afford a yellow residue. The aqueous phase still contained product, so thewater was evaporated to give a yellow solid. The solid was taken up in MeOH and DCM and filtered to remove all salts. The filtrate was evaporated to give a yellow residue. A total of two crops were obtained - one from the extraction and one from the aqueous layer. Each crop was purified by flash chromatography and combined to give 77A (off- white solid, 0.968 g, 8.87 mmol, 79 percent yield). ‘H NMR (400MHz, CHLOROFORM-d) ö8.14 (s, 2H), 3.60 (br. s., 2H), 2.61 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Preparation 10: 3-(2-methyl-5-pyrimidinyl)-1H-pyrrole-2,5-dione (P10)The title compound can be prepared by reacting <strong>[39889-94-6]2-methyl-5-pyrimidinamine</strong> with maleimide in analogy with a conventional Meerwein reaction (J. Am. Chem. Soc. 1955, 77, 2313) or variations (e.g. J. Org.. Chem., 1977, 42, 2431). To 2-methyl-5- pyrimidinamine (1 eq.) a solution of hydrochloric acid (37%, 2.6 eq.) and water should be added at room temperature with vigorous stirring and the formed precipitate should be allowed to stir for 30 minutes. Temperature should be reduced to 0 0C and sodium nitrite (1.1 eq.) in water added dropwise to the stirred suspension. At the end of diazotization, a clear solution should generally be obtained. Maleimide (2 eq.) in acetone should be added dropwise at 0 0C and then the pH of the solution adjusted to 3-3.5 by adding sodium acetate. Copper (II) chloride (0.15 eq.) should be added and vigorous stirring continued for 1 h at 0 0C then overnight at room temperature. Acetone should be removed in vacuo, the residue filtered and dried overnight in vacuo to give the title crude compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | c) 3-hydroxy-l-(2-methylpyrimidin-5-yl)-4-[4-(propan-2-yl)phenyllcarbonyl|-5-[4- (trifluoromethoxy)phenyll-2,5-dihydro-lH-pyrrol-2-one; A suspension of 4-(trifluoromethoxy)benzaldehyde (523 mg; 2.75 mmol; 1 eq) and 2- methylpyrimidin-5-amine (300 mg; 2.75 mmol; 1 eq) in EtOH (12 mL) and AcOH (cat.) was stirred at room temperature for 15 minutes before adding ethyl 2,4-dioxo-4-[4- (propan-2-yl)phenyl]butanoate of example l a (721 mg; 2.75 mmol; 1 eq). The reaction mixture was refluxed for 16 hours. Then the resulting solid was filtered and washed with diethyl ether to give the title compound, 3-hydroxy-l-(2-methylpyrimidin-5-yl)-4- { [4-(propan-2-yl)phenyl] carbonyl } -5 - [4-(trifluoromethoxy)phenyl] -2, 5 -dihydro- 1H- pyrrol-2-one in 17% yield as a white solid.1H-NMR (DMSO-de): delta (ppm) 1.21 (d, 6H); 2.51 (s, 3H); 2.95 (quint., 1H); 6.47 (s, 1H); 7.22 (d, 2H); 7.34 (d, 2H); 7.63 (d, 2H); 7.69 (d, 2H); 8.97 (s, 2H); MS (ESI+): m/z = 498.2 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water; potassium carbonate; In 1,4-dioxane; for 16h;Reflux; | To the crude product in solution in dioxane (25 mL) was added an aqueous solution of potassium carbonate 5% (40 mL). The reaction mixture was refluxed for 16 hours then cooled to room temperature. A saturated solution of sodium chloride (100 mL) was added and the aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with a saturated solution of sodium chloride (25 mL), dried over sodium sulphate and concentrated to dryness. The title compound, 2-methylpyrimidin-5-amine was obtained in 26% yield a beige solid.1H- MR (CDC13): delta (ppm) = 2.6 (s, 3H), 3.59 (br s, 2H), 8.13 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In N,N-dimethyl-formamide; toluene; at 140℃; for 0.333333h;Microwave irradiation; | A mixture of 2-bromo-N-ieri-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3- b]pyrazine-7-carboxamide (150 mg, 351 muiotaetaomicron), <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (57.4 mg, 526 muiotaetaomicron), BINAP (10.9 mg, 17.5 muiotaetaomicron), palladium (II) acetate (19.7 mg, 87.7 muiotaetaomicron) and sodium iert-butoxide (84.3 mg, 877 muiotaetaomicron) in DMF (1 mL) and toluene (500 mu) was heated in a microwave at 140C for 20 min. The reaction mixture was diluted with water then extracted into ethyl acetate (3x). The combined organic extracts were washed with brine then dried over magnesium sulfate. Purification by chromatography (silica, 40-80 % ethyl acetate in hexanes) gave N-ieri-butyl-2-(2-methylpyrimidin-5-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H- pyrrolo[2,3-b]pyrazine-7-carboxamide (78 mg, 171 muiotaetaomicron, 49 %) as a brown solid. MS (EI/CI) m/z 456.2 [M + H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77. Example 77 was prepared following the procedure for Example 1 Method B, using the enantiomer of 11, except for the urea formation and hydrolysis: To a solution of the enantiomer of 11(0.0255 g, 0.077 mmol) in THF (1.180 ml) was added 4-nitrophenylcarbonochloridate (0.0 17 g, 0.084 mmol). The reaction was stirred at rt for 30 mm. To this reaction mixture were added 77A (0.025 g, 0.230 mmol) and triethylamine (0.032 ml, 0.230 mmol). The reaction was heated at 50 C overnight, then allowed to cool to rt. The reaction was diluted with H20 and diluted with EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (3X). The organic phases were combined, dried over anhydrous Na2SO4, filtered and concentrated to give (1 S,2R)-ethyl 2-(4-(diisobutylamino)-3 -(3 -(2-methylpyrimidin-5 - yl)ureido)phenyl)cyclopropanecarboxylate as a yellow residue. The crude product wasused in the subsequent procedure. LC-MS Anal. Calc?d for C26H37N503 467.29, found[M+H] 468.3, T = 1.75 mm (Method C). To a solution of (1S,2R)-ethyl 2-(4-(diisobutylamino)-3 -(3 -(2-methylpyrimidin-5 -yl)ureido)phenyl)cyclopropanecarboxylate(0.036 g, 0.077 mmol) in tetrahydrofuran (0.171 ml) and MeOH (0.086 ml) was added1.5M lithium hydroxide aqueous solution (0.5 13 ml, 0.770 mmol). The mixture washeated at 50 C for 16 h. The reaction was neutralized with 1 N HC1 (0.77 mL) and diluted with EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (3X). The organic phases were combined and the solvent was evaporated to give the crude product as a yellow residue. Purification by preparative HPLC gave Example 77 (0.0 17 g, 0.03 8 mmol, 50%). LC-MS Anal. Calc?d for C24H33N503 439.26, found[M+H] 440.2, T = 1.31 mm (Method C). ?H NMR (500MHz, METHANOLd 4:CHLOROFORM-d) oe 8.89 (s, 2H), 7.91 (s, 1H), 7.10 (d, J=7.9 Hz, 1H), 6.98 (dd, J8.4, 1.5 Hz, 1H), 2.69 - 2.63 (m, 6H), 2.63 - 2.56 (m, 1H), 2.12 - 2.03 (m, 1H), 1.77 - 1.60 (m, 3H), 1.35 (td, J=8.2, 5.0 Hz, 1H), 0.90 (d, J=6.9 Hz, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 140℃; for 17h; | The mixture of mono-sufone (50.6 mg, 0.1 mmol), <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (109 mg, 1.0 mmol), and K2CO3 (138.1 mg, 1.0 mmol) in NMP (0.5 mL) was heated to 140 C for 17 hrs, cooled to room temperature, and TFA (15 mL) was added and stirred for 5 minutes. After removal of the solvent, prep-HPLC of the residue gave the desired product. MS (ESI) m/z 435 (M + H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With pyridine; dmap; In tetrahydrofuran; at 60℃; for 4h; | To a solution of 488A (140 mg, 0.280 mmol) in THF (6 mL) was added pyridine (0.057 mL, 0.701 mmol) and a catalytic amount of DMAP (3.42 mg, 0.028 mmol). To the above reaction mixture <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (36.7 mg, 0.336 mmol) was added and stirred at 60 C. for 4 h. The reaction mixture was concentrated and the residue was portioned between ethyl acetate (2*50 mL) and water (50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash silica column chromatography using 0-40% EtOAc in pet ether as an eluent to afford 488B (pale yellow liquid, 100 mg, 0.213 mmol, 76% yield). LC-MS Anal. Calc'd. for C25H35N5O4, 469.5. found [M+H] 470.2, Tr=2.59 min (Method N). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In N,N-dimethyl-formamide; at 100℃; for 24h;Inert atmosphere; | A mixture of compound 195 (1 equiv) and cesium carbonate (2 equiv) in DMF (20 vol) was purged with argon in a pressure vessel for 5 min, and then tris(dibenzylideneacetone) dipalladium(O) (0.01 equiv) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.01 equiv) are added under argon. The resulting mixture was stirred at 100 C for 24 h. The reaction mixture was then cooled to RT and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (MeOH/DCM) to give compound 196. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.21 g | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; for 1h;Reflux; | A mixture of 3-(t-butoxy)-3-oxopropionic acid (CAS No, 40052-13-9) (1.61 g, 10.1 mmol, 1.1 equivalents), <strong>[39889-94-6]2-methyl-5-pyrimidinamine</strong> (CAS No. 39889-94-6) (1.00 g, 9.16 mmol, 1.0 equivalent), triethylamine (1.53 mL, 11.0 mmol, 1.2 equivalents), EDC (2.11 g, 11.0 mmol, 1.2 equivalents) and DCM (20 mL) was heated to reflux for 1 hour. The reaction mixture was cooled down to room temperature, then a saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with DCM. The organic layer was concentrated under reduced pressure. The residue was purified with silica gel column chromatography (silica gel, 50%-100% ethyl acetate/n-heptane) to afford the title compound (2.21 g). 1H-NMR (400 MHz, CDCl3) delta (ppm): 1.53 (s, 9H), 2.72 (s, 3H), 3.43 (s, 2H), 8.91 (s, 2H), 9.64 (br. s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With pyridine; In dichloromethane; at 20℃; for 1h; | Intermediate 103A (170 mg) in DCM (2 mL) was added to <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (46.2 mg, 0.423 mmol) in DCM (1 mL), followed by addition of pyridine (0.14 mL, 1.76 mmol). The reaction mixture was stirred at room temperature for lh, at which time LCMS indicated a completion of reaction. The reactionmixture was diluted with EtOAc, washed with 0.5 N HC1. The organic layer was washed with brine, dried over sodium sulfate and concentrated. The crude was dissolved in DMSO and purified via preparative LC/MS (method A, 50-100% B over 10 minutes, then a 2-minute hold at 100% B). Fractions containing the desired product were combined and dried via centrifugal evaporation to yield Example 103 (80 mg, 43% yield) as a solid. ?HNMR (400MHz, chloroform-d) 8.78 (s, 2H), 8.63 (d, J1.5 Hz, 1H), 8.56 (s, 1H), 7.77(d, J0.9 Hz, 1H), 7.69 (d, J8.6 Hz, 1H), 7.13 (d, J=8.8 Hz, 1H), 4.64-4.49 (m, 4H), 4.32(dd, J=11.4, 6.6 Hz, 1H), 4.14 (s, 3H), 2.73 (s, 3H), 2.66 (s, 3H). LC-MS: method C, RT= 2.37 mm, MS (ESI) mlz: 531.1 (M+H) Analytical HPLC purity: 95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With pyridine; In dichloromethane; at 20℃; for 1h; | Intermediate 144G (540 mg, 1.222 mmol) in dichloromethane (12 mL) was added to a solution of <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (267 mg, 2.444 mmol) and pyridine (0.791 mL, 9.78 mmol) in dichloromethane (8 mL) dropwise. The reaction mixture was stirred at room temperature for 1 h, at which time LCMS and HPLC indicated a completion ofreaction. The reaction mixture was diluted with dichloromethane (20 mL) and quenched with 0.5 N HC1 (20 mL). After stirring at room temperature for 10 mm, the mixture was extracted with dichloromethane (3 X 50 mL). The organic layer was washed with brine,dried over sodium sulfate. After evaporation of solvent, the cmde product was triturated with EtOAc, the precipitate was collected by filtration, rinsed with EtOAc, dried under vacuum to give 410 mg product. The filtrate was concentrated, purified by flash chromatography (loading in chloroform/THF, 30% to 100% EtOAc in hexane over 10mm using a 12 g silica gel cartridge). The desired fractions were combined and concentrated to yield additional 80 mg product. The products were combined and lyophilized to give Example 144 (483 mg, 0.920 mmol, 75 % yield) as a yellow lyophilate. ?H NMR (500MHz, DMSO-d6) 10.09 (br. s., 1H), 8.74 (s, 3H), 8.58 (d, J=1.4 Hz, 1H), 7.91 (d, J=8.8 Hz, 1H), 7.81 (s, 1H), 7.08 (d, J=8.5 Hz, 1H), 5.35-5.26 (m,1H), 4.51 (dd, J=12.1, 2.8 Hz, 1H), 4.38 (dd, J12.1, 6.9 Hz, 1H), 4.08 (s, 3H), 3.57 (dd,J=15.7, 9.6 Hz, 1H), 3.29-3.25 (m, 1H), 2.63 (s, 3H), 2.53 (br. s., 3H). LC-MS::MethodH, 2 to 98% B. RT = 0.95 mm, MS (ESI) m/z: 515.10(M+H). Analytical HPLC purity(method B): 98%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Intermediate 145D (0.2 g, 0.658 mmol) was dissolved in THF (13.15 mL).Phosgene solution (15% in toluene, 5.01 mL, 6.58 mmol) was then added. After stirring for 2 days, the reaction mixture was concentrated in vacuo and stored on HIVAC for 3hours. The reaction mixture was dissolved in THF (13.2 mL).2-Methylpyrimidin-5-amine (0.086 g, 0.789 mmol) and pyridine (0.532 mL, 6.58 mmol) were then added. After stirring overnight, the reaction mixture was concentrated invacuo. The crude material was purified by column chromatography (ISCO, 40 g silica gel column, 19 minute gradient from 0 to 100% EtOAc in hexanes) to give Intermediate1-45 (213 mg, 0.541 mmol, 82%) as a white solid: ?H NMR (400MHz,CHLOROFORM-d) 8.74 (br. s., 2H), 7.57 (d, J=10.3 Hz, 1H), 6.70 (br. s., 1H),5.38-5.31 (m, 1H), 4.57 (dd, J12.1, 3.1 Hz, 1H), 4.44 (dd, J=12.0, 6.3 Hz, 1H), 3.52 (dd, J=15.7, 9.8 Hz, 1H), 3.21 (dd, J=16.0, 7.2 Hz, 1H), 2.70 (s, 3H); LC-MS: Method H, RT = 0.96 mm, MS (ESI) m/z: 395.0 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.6% | With pyridine; In dichloromethane; at 20℃; for 0.5h; | Intermediate 14SF (324 mg, 0.70S mmol) in dichloromethane (6 mL) was added to a solution of 2-methylpyrimidin-S-amine (1S4 mg, 1.409 mmol) and pyridine (0.4S6 mL, 5.64 mmol) in dichloromethane (3 mL) dropwise. The reaction mixture was stirred at room temperature for 0.S h, at which time LCMS and HPLC indicated a completion ofreaction. The reaction mixture was quenched with 0.S N HC1 (10 mL). Dichloromethane was removed under vacuum. The suspension was poured into a stirred solution of isopropanol. The precipitate formed was collected by filtration, washed with water and isopropanol and dried under house vacuum overnight. The product was further triturated in MeOH, sonicated, centrifuged. MeOH was removed and the solid was collected togive Example 14S (278 mg, 0.S12 mmol, 72.6 % yield) as a pale yellow solid. ?H NMR (500MHz, THF) oe 9.OS (br. s., 1H), 8.61 (d, J=1.4 Hz, 3H), 8.44 (s, 1H), 7.66 (dd, J1.8, 1.0 Hz, 1H), 7.S7 (d,J=11.OHz, 1H), S.29-S.21 (m, 1H), 4.4S (dd,J12.1, 3.0 Hz, 1H), 4.33 (dd, J12.2, 6.2 Hz, 1H), 3.99 (s, 3H), 3.56-3.50 (m, 1H), 3.26 (dd, J=15.5, 7.6 Hz,1H), 2.53 (s, 3H), 2.43 (s, 3H). ?9F NMR (471MHz, THF) -140.57 (s, iF). LC-MS:Method H, 0 to 100% B. RT = 1.97 mm, MS (ESI) m/z: 533.2 (M+H). AnalyticalHPLC purity (method B): 98%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48.3% | With pyridine; In dichloromethane; at 20℃; for 1h; | Intermediate 150A (54 mg, 0.122 mmo) in dichoromethane (2 mL) was added to a soution of 2-methypyrimidin-5-amine (26.7 mg, 0.244 mmo) and pyridine (0.079 mL,0.978 mmo) in dichoromethane (1.0 mL) dropwise. The reaction mixture was stirred at room temperature for 1 h, at which time LCMS and HPLC indicated a competion ofreaction. The reaction mixture was diuted with dichoromethane (20 mL) and quenched with 0.5 N HC1 (2 mL). After stirring at room temperature for 10 mm, the mixture was extracted with dichoromethane. The organic ayer was washed with brine, dried oversodium sufate. After evaporation of sovent, the crude product was purified viapreparative LC/MS (method A, 55-100% B over 10 minutes, then a 2-minute hod at100% B). Fractions containing the desired product were combined and dried viacentrifuga evaporation, then yophiized to yied the Exampe 150 (31 mg, 0.059 mmo,48.3 % yied) as ayeow yophiate. ?H NMR (500MHz, acetone) 9.85 (br. s., 1H),8.71 (br. s., 2H), 8.57 (s, 1H), 8.55 (d, J=1.9 Hz, 1H), 7.80 (d, J=8.8 Hz, 1H), 7.70 (s,1H), 6.96 (d, J=8.8 Hz, 1H), 5.29-5.22 (m, 1H), 4.47 (dd, J12.1, 3.0 Hz, 1H), 4.35 (dd, J=12.0, 6.5 Hz, 1H), 4.02 (s, 3H), 3.53 (dd, J15.7, 9.9 Hz, 1H), 3.27 (dd, J15.7, 7.4 Hz, 1H), 2.56 (s, 3H), 2.43 (s, 3H). LC-MS: Method H, 2 to 98% B. RT = 2.08 mm, MS (ESI) m/z: 515.2 (M+H) Analytical HPLC purity (method B): 98%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17 mg | With pyridine; In dichloromethane; at 20℃; for 0.5h; | Intermediate 151C (63 mg, 0.136 mmo) in dichloromethane (2 mL) was added toa solution of <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (22.24 mg, 0.204 mmol) and pyridine (0.088 ml,1.087 mmol) in dichloromethane (2 mL) dropwise. The reaction mixture was stirred at room temperature for 0.5 h, at which time LCMS and HPLC indicated a completion of reaction. The reaction mixture was quenched with 0.5 N HC1 (2 mL) and extracted with DCM. The combined organic layer was washed with iN HC1, NaHCO3 and brine, driedwith Mg504 and concentrated. The crude was purified with a 40g ISCO column eluted with 0-100% EtOAc/DCM for 20 mm. The desired fractions were collected andconcentrated to give 20 mg of desired product. The product was further purified using apreparative HPLC (method A, 55-100% B over 10 minutes, then a 2-minute hold at 100%B). Fractions containing the desired product were combined and dried via centrifugalevaporation, then lyophilized to yield the Example 151 (17 mg) as ayellow lyophilate. ?HNMR (500MHz, THF) 9.16 (br. s., 1H), 8.72 (s, 3H), 8.56 (s, 1H), 7.77 (s, 1H), 7.68 (d,J=11.0 Hz, 1H), 5.41-5.31 (m, 1H), 4.60-4.39 (m, 2H), 4.10 (s, 3H), 3.68-3.61 (m, 1H),3.38 (dd, J15.7, 7.4 Hz, 1H), 2.64 (s, 3H), 2.53 (s, 3H). ?9F NMR (376JV1Hz,CHLOROFORM-d) -142.43 (s, iF). LC-MS: Method H, 0 to 100% B. RT = 1.02 mm,MS (ESI) m/z: 533.15 (M+H)t Analytical HPLC purity (method B): 99% purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; In dichloromethane; at 0℃; for 1h; | Intermediate 153C (30 mg, 0.063 mmol) in dichloromethane (1.0 mL) was addedto a solution of <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (13.82 mg, 0.127 mmol) and pyridine (0.041mL, 0.506 mmol) in dichloromethane (1.0 mL) dropwise. The reaction mixture was stirred at room temperature for 1 h, at which time LCMS and HPLC indicated a completion of reaction. The reaction mixture was quenched with 0.5 N HC1 (5 mL) and extracted with dichloromethane. The organic layer was washed with brine, dried oversodium sulfate and concentrated. The crude product was triturated with MeOH (2X), spun in a centrifuge. The liquid was removed and the solid was collected, dried and lyophilized to give Example 153 (20 mg, 0.034 mmol, 53.8 % yield) as a slightly yellow lyophilate. ?H NMR (500MHz, THF) 8.60 (d, J1.7 Hz, 3H), 8.44-8.40 (m, 1H), 7.63 (d, J0.8 Hz, 1H), 7.57 (d, J10.7 Hz, 1H), 5.29-5.22 (m, 1H), 4.49-4.42 (m, 3H), 4.33(dd,J=12.2, 6.2 Hz, 1H), 3.56-3.51 (m, 1H), 3.27 (dd,J15.1, 7.4 Hz, 1H), 2.53 (s, 3H),2.43 (s, 3H), 1.37 (t, J=7.0 Hz, 3H); LC-MS: Method A, 40 to 100% B. RT = 2.21mm, MS (ESI) m/z: 547.2(M+H). Analytical HPLC purity (method B): 93% purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.6% | With pyridine; In dichloromethane; at 20℃; for 0.5h; | Intermediate 174A (10mg, 0.021 mmol) in dichloromethane (1 mL) was added to a solution of <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (4.61 mg, 0.042 mmol) and pyridine (0.017 ml, 0.211 mmol) in dichloromethane (0.5 mL) dropwise. The reaction mixture was stirred at room temperature for 0.5 h, at which time LCMS and HPLC indicated a completion of reaction. The reaction mixture was diluted with EtOAc, washed with 0.5 N HC1. The organic layer was washed with brine, dried over sodium sulfate and concentrated. Thecrude was dissolved in DMSO and purified via preparative LC/MS (Method D: Gradient:45-90% B over 10 minutes, then a 5-minute hold at 100% B). Fractions containing the desired product were combined and dried via centrifugal evaporation to Example 174 (7.8 mg, 0.014 mmol, 67.6 % yield). ?H NMR (500MHz, DMSO-d6) 10.02 (br. s., 1H), 8.72 (s, 3H), 8.56 (s, 1H), 7.85 (d, J=11.3 Hz, 1H), 7.81 (s, 1H), 4.49-4.32 (m, 2H), 4.07 (s,3H), 3.57-3.29 (m, 2H), 2.62 (s, 3H), 2.54 (s, 3H), 1.60 (s, 3H). LC-MS: Method L, 0 to100% B. RT = 2.27 mm, MS (ESI) m/z: 547.15 (M+H). Analytical HPLC purity (method B): 100%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.8% | With pyridine; In dichloromethane; at 20℃; for 0.5h; | Intermediate 182A (10 mg, 0.021 mmol) in dichloromethane (1 mL) was added toa solution of <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (4.61 mg, 0.042 mmol) and pyridine (0.017 ml,0.211 mmol) in dichloromethane (0.5 mL) dropwise. The reaction mixture was stirred atroom temperature for 0.5 h, at which time LCMS and HPLC indicated a completion ofreaction. The reaction mixture was diluted with EtOAc, washed with 0.5 N HC1. Theorganic layer was washed with brine, dried over sodium sulfate and concentrated. Thecrude was dissolved in DMSO and purified via preparative LC/MS (Method D: Gradient:45-90% B over 10 minutes, then a 5-minute hold at 100% B). Fractions containing the desired product were combined and dried via centrifugal evaporation to Example 182 (8.4 mg, 0.015 mmol, 72.8 % yield). ?H NMR (500MHz, DMSO-d6) 8.73 (s, 3H), 8.56 (s,1H), 7.94-7.72 (m, 2H), 4.53-4.29 (m, 2H), 4.07 (s, 3H), 3.63-3.19 (m, 1H), 2.62 (s, 3H),1.60 (s, 3H). LC-MS: Method L, 0 to 100% B. RT = 2.27 mm, MS (ESI) m/z: 547.15 (M+H) Analytical HPLC purity (method B): 100%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34.5% | With pyridine; In dichloromethane; at 20℃; for 0.5h; | To Intermediate 194A (10 mg, 0.022 mmol) in dichloromethane (1 mL) was added to a solution of <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (4.79 mg, 0.044 mmol) and pyridine (0.018 ml, 0.219 mmol) in dichloromethane (0.5 mL) dropwise. The reaction mixture was stirred at room temperature for 0.5 h, at which time LCMS and HPLC indicated acompletion of reaction. The reaction mixture was diluted with EtOAc, washed with 0.5 NHC1. The organic layer was washed with brine, dried over sodium sulfate andconcentrated. The crude was dissolved in DMSO and purified via preparative LC/MS(Method D: Gradient: 45-90% B over 20 minutes, then a 5-minute hold at 100% B).Fractions containing the desired product were combined and dried via centrifugalevaporation to Example 194 (4.0 mg, 7.57 iimol, 34.5 % yield). ?H NMR (500MHz,DMSO-d6) oe 10.01 (br. s., 1H), 8.73 (br. s., 3H), 8.57 (br. s., 1H), 7.90 (d, J8.2 Hz, 1H), 7.80 (br. s., 1H), 7.04 (d, J8.5 Hz, 1H), 4.48-4.27 (m, 2H), 4.07 (s, 3H), 3.56-3.15 (m, 2H), 2.62 (s, 3H), 2.54 (s, 3H), 1.55 (s, 3H). LC-MS: Method L, 0 to 100% B. RT = 2.20 mm, MS (ESI) m/z: 529.35 (M+H)t Analytical HPLC purity (method B): 100%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | Intermediate 287D (0.292 g, 1.133 mmol) was dissolved in THF (22.7 mL). Phosgene solution (15% in toluene, 8.64 mL, 11.33 mmol) was then added. After 2 days, the reaction mixture was concentrated in vacuo and stored on HIVAC for 3 hours. The reaction mixture was dissolved in THF (22.7 mL). 2-Methylpyrimidin-5-amine (0.148 g, 1.36 mmol) and pyridine (0.916 mL, 11.3 mmol) were added. After stirring overnight,the reaction mixture was concentrated in vacuo. The cmde material was purified bycolumn chromatography (ISCO, 40 g silica gel column, 19 minute gradient from 0 to100% EtOAc in hexanes) to give Intermediate 1-42 (260 mg, 0.66 mmol, 58%) as a whitesolid: ?H NMR (400MHz, CHLOROFORM-d) 8.75 (br. s., 2H), 7.49 (d, J=8.8 Hz, 1H),7.08 (d, J=8.8 Hz, 1H), 6.71 (br. s., 1H), 4.58-4.45 (m, 4H), 4.24 (dd, J=1 1.3, 6.7 Hz,1H), 2.72 (s, 3H); LC-MS: Method H, RT = 0.97 mm, MS (ESI) m/z: 393.1 (M+H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34.6% | With pyridine; In dichloromethane; at 20℃; for 0.5h; | Intermediate 292A (69 mg, 0.145 mmo) in dichloromethane (2 mL) was added to a solution of <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (31.7 mg, 0.290 mmol) and pyridine (0.094 ml,1.161 mmol) in dichloromethane (2 mL) dropwise. The reaction mixture was stirred at room temperature for 0.5 h, at which time LCMS and HPLC indicated a completion of reaction. The reaction mixture was quenched with 0.5 N HC1 (2 mL) and extracted with DCM. The combined organic layer was washed with iN HC1, NaHCO3 and brine, dried with Mg504 and concentrated. The crude was purified with a 40g ISCO column elutedwith 0-100% EtOAc/DCM for 20 mm. The desired fractions were collected and concentrated to give 20 mg of desired product. The product was further purified using a preparative HPLC (method A, 65-100% B over 10 minutes, then a 2-minute hold at 100%B). Fractions containing the desired product were combined and dried via centrifugal evaporation, then lyophilized to yield the Example 292 (35 mg, 34.6% yield) as a yellowlyophilate. ?H NMR (400MHz, CHLOROFORM-d) 8.77 (s, 2H), 8.63 (d, J1.8 Hz,1H), 8.55 (s, 1H), 7.77 (s, 1H), 7.54 (d, J=10.8 Hz, 1H), 6.86-6.75 (m, 1H), 4.65 (d, J=4.6Hz, 1H), 4.60-4.54 (m, 3H), 4.36 (dd,J=11.6, 6.7 Hz, 1H), 4.14 (s, 3H), 2.72 (s, 3H), 2.66(s, 3H). ?9F NMR (376 MHz, CHLOROFORM-d) -136.02 (s, iF). LC-MS: Method H,0 to 100% B. RT = 2.49 mm, MS (ESI) m/z: 549.2 (M+H). Analytical HPLC purity(method B): 95% purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; toluene; at 20℃; | To a suspension of <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (68 mg, 0.623 mmol) in DCM (10 ml) was added phosgene (15% in toluene) (2.197 ml, 3.12 mmol) followed by addition ofDIEA (0.163 ml, 0.93 5 mmol) dropwise. The mixture was stirred at room temperature overnight. Solvent was removed under vacuum to give Intermediate 79A as a yellow solid. It was used for next step without further purification. LC-MS: method C, RT = 0.57 mm, MS (ESI) m/z: 154 (M+H) (methyl carbamate). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14.5% | Example 020D (29 mg, 0.061 mmol) was dissolved in anhydrous THF (3 ml) and was treated with phosgene (0.434 ml, 0.609 mmol) at room temperature for 4 days. Then solvent was removed and the residue was dissolved in DCM (3 mL). <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (26.6 mg, 0.243 mmol) was added, followed by pyridine (0.025 ml, 0.304 mmol). The mixture was stirred at room temperature for 2 hours. The solvent was removed in vacuo and residue was purified on preparative HPLC with method D and dried to give Example 020 (5.5 mg, 0.008 mmol, 14.5%) as the product, 1H NMR (500 MHz, DMSO-d6) delta ppm 9.95 (1 H, br s), 8,64 (2 H, m), 8.56 (1 I I. s), 8.42 (1 I I. s), 8.34 (1 H, d, J = 10.68 Hz), 7.75 (1 H, s), 5.65 (1 H, m), 5.36 (1 H, m), 4,04 (3 H, s), 2,62 (2 H, d, J =13.73 Hz), 2,57 (3H, s), 2.43 (3 I I. s), 2, 16 (3 H, m), 1.95 (1 H, m.); 19F NMR (471 MHz, DMSO-6) delta ppm -88,9 (2 F, m), -139.81 (1 F, br s); LC-MS: method L, RT = 2.483 min, MS (ESI) m/z: 612.30 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31.4% | With pyridine; In dichloromethane; at 20℃; for 1h; | In a vial charged with a stirring bar, Intermediate 018C (22.5 mg, 0.041 mmol) was dissolved in DCM (2 ml.). 2-raethylpyriraidin-5-araine (1 7.79 mg, 0. 163 ramol) was added, followed by pyridine (0.016 mL, 0.204 mmol). The mixture was stirred at room temperature for 1 hour. The crude material was purified via preparative LC/MS Method C: Fractions containing the desired product were combined and dried via centrifugal evaporation to give Example 018 ( 8.0 mg, 0,013 mmol, 31.4% yield) as the title compound. NMR (500 MHz, CDCb) 6 ppm 8.83 (2 H, s), 8.57 (1 I I. d, .7=1.65 Hz), 8.49 (1 H, s), 7.80 (2 H, O. J i i 28 Hz), 7.71 (1 H, s), 7,57 (1 H, d. ./ 7.70 Hz), 5.42 (1 H, br s), 4.56 (3 H, q, J=6.97 Hz), 2.71 (3 H, s), 2.62 - 2.63 (3 H, ml 2.51 - 2.59 (1 I I. m), 2.36 - 2.51 ( 1 I I. m), 2.29 (1 H, d, ./ 14 3 f Hz), 2.06 (2 H, br s), 1.85 (1 H, br s), 1.50 (3 H, t,J = 7.02 Hz); 19F NMR (471 MHz, CDC ) delta ppm -100.34 to -72.99 (2 F, m), -132.45 (1 F, d, J=8.58 Hz): LC-MS: method L, RT = 2.53 ram, MS (ESI) m/z: 625. 15 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
327 mg | Intermediate I-72A (300 mg, 0.937 mmol) was dissolved in THF (18.7 mL). Phosgene solution (15% in toluene, 7.14 mL, 9.37 mmol) was then added. After stirring overnight, the reaction mixture was concentrated in vacuo and stored on HIVAC for 3 hours. The reaction mixture was dissolved in THF (18.7 mL). 2-Methylpyrimidin-5-amine (123 mg, 1.12 mmol) and pyridine (758 tL, 9.37 mmol)were added. After 1 hour, the reaction mixture was concentrated in vacuo and purified bycolumn chromatography (ISCO, 24 g silica gel column, 19 minute gradient from 0 to100% EtOAc in hexanes) to give Intermediate 1-13 0 (327 mg, 0.796 mmol, 85%) as awhite solid: ?H NMR (400MHz, CDC13) 8.72 (br. s., 2H), 7.66 (d, J=11.0 Hz, 1H), 7.36(d,J7.7 Hz, 1H), 6.55 (br. s., 1H), 5.14 (dd,J6.5, 3.0 Hz, 1H), 4.60-4.49 (m, 1H), 2.71(s, 3H), 1.44 (d, J=6.6 Hz, 3H), 1.40 (d, J=6.4 Hz, 3H); LC-MS: Method H, RT = 0.95mm, MS (ESI) m/z: 411.0 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8% | To a mixture of crude Intermediate 520B (12 mg, 0.022 mmol) and DIPEA (0.057 mL, 0.329 mmol) in THF (1 mL) was added 15% phosgene in toluene (0.108 mL, 0.154 mmol) at room temperature. The solution immediately became smoky and deposited white salts. After 10 mi <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (7.18 mg, 0.066 mmol) and silver nitrate (18.64 mg, 0.110 mmol) were added. The reaction mixture was then sealed andheated to 65 C for 1 h. The resulting reaction mixture was cooled to room temperature, diluted with EtOAc, filtered over Celite, concentrated and purified by prep HPLC (Method D, 40-75% over 25 mm, hold 100% for 7mm) to afford Example 520 (1.1 mg, 0.002 mmol, 8% yield) as a yellow solid over the two step sequence. LC-MS. Method H, RT = 1.15 mm, MS (ESI) m/z: 568.3, 570.2 (M+H). ?HNMR(SOOIVIHz, DMSO-d6)8.76 (s, 2H), 8.69 (s, 1H), 8.55 (s, 1H), 7.95 (d, J=7.3 Hz, 1H), 7.81 (s, 1H), 4.34 (br. s.,2H), 4.07 (s, 3H), 3.81 (br. s., 2H), 3.11 (s, 3H), 2.63 (s, 3H), 2.52 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
182 mg | With pyridine; In tetrahydrofuran; for 0.166667h; | To a solution of Intermediate I-72B (170 mg, 0.332 mmol) in THF (6.5 mL) was added a 15% phosgene solution in toluene (2354 p1, 3.34 mmol). The resulting slurrywas allowed to stir at room temperature for 16 h before being concentrated down to the crude chloroformate intermediate. This crude residue was retaken in THF (6.5 mL) and <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (39.9 mg, 0.365 mmol) followed by pyridine (0.134 mL,1.660 mmol) were added to the reaction mixture. After 10 mm, the reaction mixture was concentrated and purified by ISCO (40g, 0-100% EtOAc/Hex, Product at 85%) to afford Intermediate 1-73 (182 mg, 0.311 mmol, 94% yield) as a yellow solid. LC-MS: MethodH, RT= 1.17 mm, MS (ESI)m/z: 585.2 (M+H)t ?HNMR(400MF-Tz,CHLOROFORM-d) 8.76 (d, J=2.0 Hz, 1H), 8.72 (br. s., 2H), 8.69 (s, 1H), 7.86-7.78(m, 2H), 7.66 (t, J=71.8 Hz, 1H), 7.53 (d, J=7.9 Hz, 1H), 6.49 (br. s., 1H), 5.21-5.12 (m,1H), 4.63 (dd, J=6.4, 3.3 Hz, 1H), 2.69 (s, 3H), 2.68 (s, 3H), 1.47 (d, J=6.6 Hz, 3H), 1.44(d, J=6.4 Hz, 3H). ?9F NMR (376MHz, CHLOROFORM-d) -89.78 (s, 3F), -132.17 (s,iF) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41.8% | With pyridine; In dichloromethane; for 1h; | 2-Methylpyrimidin-5-amine (13.73 mg, 0.126 mmol) and pyridine (0.068 mL,0.839 mmol) were dissolved in DCM (3 mL). Intermediate 813C (40 mg, 0.084 mmol) was added as a solution in DCM (1 mL). The reaction mixture was allowed to stir for 1 hour. The reaction mixture was concentrated under reduced pressure and purified by ISCO using a 12 g column with a 0-100% EtOAc in hexanes gradient to yield Example 813 (0.0203 g, 0.035 mmol, 41.8 %yield) as a yellow solid. ?HNMR(400IVIHz, CDC13)8.74 (br. s., 2H), 8.55 (t, J=2.3 Hz, 1H), 8.50 (d, J=2.6 Hz, 1H), 8.01 (s, 1H), 7.98 (d,J=0.9 Hz, 1H), 7.74 (s, 1H), 6.55 (br. s., 1H), 5.75 (dd, J=6.5, 3.4 Hz, 1H), 5.39 (dd,J=6.5, 3.4 Hz, 1H), 4.57 (d, J=7.0 Hz, 3H), 2.64 (s, 3H), 1.52 (d, J=1.5 Hz, 3H), 1.50 (s,3H), 1.48 (d, J=1 .5 Hz, 3H). LC-MS. method H, RT = 1.27 mm, MS (ESI) m/z: 550.1(M+H). Analytical HPLC Method B: 95% purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28.8% | With pyridine; In tetrahydrofuran; dichloromethane; at 20℃; for 1h; | To a solution of Intermediate 1-132 (17 mg, 0.037 mmol) in DCM (1 mL) and THF (0.5 mL) was added <strong>[39889-94-6]2-methylpyrimidin-5-amine</strong> (8.02 mg, 0.073 mmol) followed by pyridine (0.030 mL, 0.367 mmol). The mixture was stirred at room temperature for 1 hour. The reaction was quenched with 0.2 mL of MeOH. The reaction mixture was concentrated and redissolved in DMF, filtered, and purified by preparative HPLC(Method D, 25 to 100% B in 20 minutes) to yield Example 678 (5.9 mg, 10.58 tmol,28.8 % yield): ?HNMR (500MHz, DMSO-d6) 9.97 (br. s., 1H), 8.71 (br. s., 2H), 8.63-8.59 (m, 1H), 8.44 (s, 1H), 8.37 (d, J=10.7 Hz, 1H), 7.77 (s, 1H), 5.26 (br. s., 1H), 4.79(d, J10.7 Hz, 1H), 4.57-4.44 (m, 1H), 4.05 (s, 3H), 3.44 (br. s., 3H), 2.58 (s, 3H), 1.40(d, J=6.4 Hz, 3H). LC-MS. method H, RT = 1.45 mm, MS (ESI) m/z: 536.2 (M+H).Analytical HPLC Method B: 96% purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With pyridine; In dichloromethane; for 1h; | 2-Methylpyrimidin-5-amine (0.023 g, 0.206 mmol) and pyridine (0.083 mL, 1.032 mmol) were dissolved in DCM (2 mL) To this solution was added Intermediate I-135A15 (0.035 g, 0.103 mmol) as a solution in DCM(1 mL). The reaction mixture was allowed to stir for lh. The reaction mixture was concentrated under reduced pressure to yield Intermediate 1-135 (0.040 g, 0.097 mmol, 94%). LC-MS: method H, RT = 1.09 mm, MS (ESI) m/z: 412.0 (M+H)t |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With pyridine; In dichloromethane; for 1h; | 2-Methylpyrimidin-5-amine (0.023 g, 0.215 mmol) and pyridine (0.083 mL, 1.032 mmol) were dissolved in DCM (2 mL) To this solution was added Intermediate I-139A(0.035 g, 0.108 mmol) as a solution in DCM (1 mL). The reaction mixture was allowed to stir for lh. The reaction mixture was concentrated under reduced pressure to yield Intermediate 1-139 (0.038 g, 0.096 mmol, 89%). LC-MS: method H, RT = 1.04 mm, MS (ESI) m/z: 398.0 (M+H). |
Tags: 39889-94-6 synthesis path| 39889-94-6 SDS| 39889-94-6 COA| 39889-94-6 purity| 39889-94-6 application| 39889-94-6 NMR| 39889-94-6 COA| 39889-94-6 structure
[ 372118-67-7 ]
Pyrimidin-2-ylmethanamine hydrochloride
Similarity: 0.79
[ 372118-67-7 ]
Pyrimidin-2-ylmethanamine hydrochloride
Similarity: 0.79
Precautionary Statements-General | |
Code | Phrase |
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P103 | Read label before use |
Prevention | |
Code | Phrase |
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P222 | Do not allow contact with air. |
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P265 | Wash skin thouroughly after handling. |
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Response | |
Code | Phrase |
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P321 | |
P322 | |
P330 | Rinse mouth. |
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P334 | Immerse in cool water/wrap n wet bandages. |
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P378 | |
P380 | Evacuate area. |
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P391 | Collect spillage. Hazardous to the aquatic environment |
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P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
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P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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