Structure of H-Sar-NH2.HCl
CAS No.: 5325-64-4
*Storage:
*Shipping:
4.5
*For Research Use Only !
Change View
Size | Price | US Stock | Global Stock | In Stock |
250mg | łÇʶÊÊ | Inquiry | Inquiry | |
1g | łÇ˶ÊÊ | Inquiry | Inquiry | |
5g | łËʶÊÊ | Inquiry | Inquiry | |
10g | łËͶÊÊ | Inquiry | Inquiry | |
25g | łÿď¶ÊÊ | Inquiry | Inquiry | |
100g | łËǧ¶ÊÊ | Inquiry | Inquiry |
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
łÇʶÊÊ
łÇ˶ÊÊ
łËʶÊÊ
łËͶÊÊ
łÿď¶ÊÊ
łËǧ¶ÊÊ
In Stock
- +
US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
CAS No. : | 5325-64-4 |
Formula : | C3H9ClN2O |
M.W : | 124.57 |
SMILES Code : | Cl.CNCC(N)=O |
MDL No. : | MFCD00058283 |
InChI Key : | VVIXOTCTYAILNP-UHFFFAOYSA-N |
Pubchem ID : | 13892956 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.67 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 29.21 |
TPSA ? Topological Polar Surface Area: Calculated from | 55.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | -0.46 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | -0.51 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | -0.8 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | -1.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | -0.56 |
Log S (ESOL):? ESOL: Topological method implemented from | -0.19 |
Solubility | 80.3 mg/ml ; 0.645 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -0.23 |
Solubility | 73.1 mg/ml ; 0.587 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -0.21 |
Solubility | 76.5 mg/ml ; 0.614 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 | No |
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) | No |
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 | -7.39 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 | 2.0 |
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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) | 1.0 |
* 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 |
---|---|---|
65% | To a solution of 3- [5-BROMO-4- [ (2, 4-difluorobenzyl) oxy]- 2-methyl-6-oxopyrimidin-1 (6H)-YL]-4-METHYLBENZOIC acid (1.0 g, 0.022 mol) in dimethylacetamide (10.0 mL) at-20 oC was added isobutylchloroformate (0.36 g, 0.0028 mol), followed by dropwise addition of N-METHYLMORPHOLINE (0.30 G, 0.003 mol) and stirred for 10 min under nitrogen atmosphere. The reaction mixture was then stirred at room temperature for 20 min, cooled to 0 oC, and added N-methylmorpholine (0.30 g, 0.003 mol) followed by the addition of N-methylglycine amide hydrochloride (0.35 G, 0.0028 mol) and DMAP (0.025 g). The reaction mixture was stirred at room temperature for 4 h, and concentrated IN VACUO. The resulting the residue was purified by reverse-phase HPLC using 10-90% CH3CN/Water gradient (40 min) at a flow rate of 80 mL/min. The appropriate fractions (MH+, m/z = 535) were combined, and freeze-dried to give a white solid. This was dissolved in dichloromethane (25 mL), washed successively with 5% sodium bicarbonate (2 x 20 mL), water (2 x 20 mL), dried (NA2SO4), and concentrated to dryness to afford the racemic title compound (0.75 g, 65%) as a white amorphous substance : 1H NMR (CD30D/400 MHz) 5 7.96 (dd 1H, J = 1.6 Hz, 8.0 Hz), 7.72 (d, 1H, J = 1.6 Hz), 7.62 (m, 1H), 7.56 (d, 1H, J = 8.0 Hz), 7.01 (m, 2H), 5.55 (abq, 2H), 3.99 (s, 2H), 2.74 (s, 3H), 2.18 (s, 3H), and 2.14 (s, 3H); ES-HRMS M/Z 535.0792 (M+H calcd for C23H22N404F2 Br requires 535. 0787). 19F NMR (CD3OD/ 400 MHz) -111. 85 (m) and - 115. 91 (m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8.5 g (52%) | With sodium hydrogencarbonate; In water; benzene; | A solution of chloroacetyl chloride (0.1 mole, 11.3 g) in benzene (40 ml) was added over 30 min to a mixture of <strong>[5325-64-4]sarcosinamide hydrochloride</strong> (0.1 mole, 12.45 g) and sodium bicarbonate (0.25 mole, 20.0 g) in 40 ml of water. The mixture was vigorously stirred for 3 h at room temperature. The aqueous phase was acidified with 5M hydrochloric acid to pH 5 and extracted with ethyl acetate (3*400 ml). The combined extracts were dried over anhydrous sodium sulphate and evaporated in vacuo. The solid residue obtained was recrystallized from ethanol-ether to give 8.5 g (52%) of the title compound. Mp 85-86 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With methylamine; | EXAMPLE 87 PREPARATION OF alpha-CHLOROACETYLSARCOSINAMIDE Sarcosinamide hydrochloride was prepared by reacting methylamine with 2-chloroacetamide as described by Marvel et al. (1946). The compound was recrystallized from ethanol. Mp 160-161 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | To a solution of carbamoylmethyl-methyl-carbamic acid t-butyl ester (848 mg, 4.50 mmol) (obtained as described in Reference Example 44(1)) in 1,4-dioxane (8.50 ml) was added a solution of 4N hydrogen chloride in 1,4-dioxane (8.50 ml) in an ice bath, and the mixture was stirred at room temperature for 2.5 hours. After checking the completion of the reaction, diethyl ether was added thereto, and the reaction mixture was stirred for 30 minutes. The resulting reaction mixture was filtered, and the obtained residue was washed with diethyl ether and dried to give 2-methylaminoacetamide hydrochloride (421 mg, yield 75%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; sodium iodide; In N,N-dimethyl-formamide; at 160℃; for 0.0833333h;Microwave irradiation; | Example 16A 7-Chloro-1-(tetrahvdropyran-4-yl)methyl-3-(4-[Lambda/-(carboxamido)methyl-Lambda/- methylaminolmethylHI ,3l-thiazol-2-yl)-1 /-/-indole A mixture of 7-chloro-3-[4-(chloromethyl)thiazol-2-yl]-1-(tetrahydropyran-4- yl)methyl-1 /-/-indole (prepared as described in Example 16, using toluene-4-sulfonic acid tetrahydropyran-4-ylmethyl ester instead of cyclohexylmethyl bromide) (40 mg, 0.10 mmol), Lambda/-methyl glycine amide hydrochloride (18.4 mg, 0.15 mmol), di- isopropylethylamine (35 mul, 0.21 mmol) and sodium iodide (16 mg, 0.10 mmol) in dimethylformamide (2 ml) was subjected to microwave irradiation for 5 min at 160 C. The reaction mixture was filtered through a 5 g Strata SCX giga tube. The tube was washed with dichloromethane and then eluted with 10% (2 M ammonia in methanol) in dichloromethane. The product was purified by column chromatography eluting with 3:97 (v/v) (2M ammonia in methanol): dichloromethane to give the title compound (39 mg, 0.09 mmol). EsIMS: m/z 433.5, 435.4 [M+H]+. | |
With N-ethyl-N,N-diisopropylamine; sodium iodide; In N,N-dimethyl-formamide; at 160℃; for 0.0833333h;Microwave irradiation; | EXAMPLE 16A 7-Chloro-1-(tetrahydropyran-4-yl)methyl-3-(4-[N-(carboxamido)methyl-N-methylamino]methyl}-[1,3]-thiazol-2-yl)-1H-indole A mixture of 7-chloro-3-[4-(chloromethyl)thiazol-2-yl]-1-(tetrahydropyran-4-yl)methyl-1H-indole (prepared as described in Example 16, using toluene4-sulfonic acid tetrahydropyran4-ylmethyl ester instead of cyclohexylmethyl bromide) (40 mg, 0.10 mmol), N-methyl glycine amide hydrochloride (18.4 mg, 0.15 mmol), di-isopropylethylamine (35 mul, 0.21 mmol) and sodium iodide (16 mg, 0.10 mmol) in dimethylformamide (2 ml) was subjected to microwave irradiation for 5 min at 160 C. The reaction mixture was filtered through a 5 g Strata SCX giga tube. The tube was washed with dichloromethane and then eluted with 10% (2 M ammonia in methanol) in dichloromethane. The product was purified by column chromatography eluding with 3:97 (v/v) (2M ammonia in methanol): dichloromethane to give the title compound (39 mg, 0.09 mmol). EsIMS: m/z 433.5, 435.4 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 20℃; for 18h; | Example 20 7-Chloro-3-[(5-[Lambda/-(carboxamido)methyl1-Lambda/-methylamino)methyl)-([1 ,2,41oxadiazol-3- vDI-1 -(tetrahydropyran-4-yl)methyl-1 /-/-indole, hydrochloride salt To a solution of 7-chloro-3-[(5-chloromethyl)-([1 ,2,4]oxadiazol-3-yl)]-1-(tetra- hydropyran-4-yl)methyl-1 /-/-indole (Example 19; Step C; 1.5 g, 4.09 mmol) in 1- methyl-2-pyrrolidinone (5 ml) was added Lambda/-methyl glycine amide hydrochloride (1.0 g, 8.19 mmol) and potassium carbonate (3.4 g, 24.6 mmol). The reaction was stirred at room temperature for 18 h before being diluted with dichloromethane (10 ml) and filtered through a 20 g Strata SCX giga tube. The tube was washed with methanol and then eluted with 2 M ammonia in methanol. The methanolic ammonia solution was evaporated to dryness. This was re-dissolved in dichloromethane, washed with water and brine, dried over sodium sulfate and the solvent removed in vacuo. The resulting residue was purified by flash column chromatography eluting with 2% (v/v) ethanol in dichloromethane. The solid was dissolved in dichloromethane and hydrogen chloride (2M solution in diethyl ether) was added. The resultant EPO <DP n="39"/>hydrochloride salt was crystallised from acetone to afford the title compound as a 1 :1 hydrochloride salt (1.24 g, 2.73 mmol). EsIMS: m/z 418.3 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetonitrile; at 150℃; for 0.5h;Microwave irradiation; | Example 5 7-Methoxy-3-[(5-[(Lambda/-carboxamido)methyl1methylamino)methyl)-([1 ,2,41-thiadiazol-3- yl)1-1-(tetrahvdropyran-4-yl) methyl-1 /-/-indole, trifluoroacetic acid salt. Methanesulfonic acid 3-(1 -tetrahydropyran-4-yl)methyl-7-methoxy-indol-3-yl)- ([1 ,2,4]thiadiazol-5-ylmethyl ester (106 mg, 0.25 mmol), prepared according to the method of Example 1 using 7-methoxyindole instead of 7-chloroindole, was dissolved in acetonitrile (2 ml) and transferred into a microwave vial. Lambda/-methyl glycine amide hydrochloride (53 mg, 1.26 mmol) and potassium carbonate (174 mg, 1.26 mmol) were added and the reaction mixture subjected to microwave irradiation at 150 C for 30 mins using an Emrys Optimizer EXP. The free base was purified by semi-prep. HPLC (Method i) to afford the title compound as a 1 :1 trifluoroacetic acid salt (17.4 mg, 0.03 mmol). EsIMS: m/z 452.1 [M+Na]+, 429.8 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In dichloromethane; at 100℃; for 0.05h;Microwave irradiation; | Example 9 7-Ethyl-3-r(5-{r/V-(carboxamido)methyll-/V-methylamino>methyl)-(ri ,2,41-thiadiazol-3- yl)1-1-(tetrahvdropyran-4-yl)methyl-1 H-indole, hydrochloride acid salt Methanesulfonic acid 3-(1 -tetrahydropyran-4-yl)methyl-7-ethyl-1 H-indol-3-yl)- ([1 ,2,4]thiadiazol-5-ylmethyl ester (30 mg, 0.07 mmol) prepared according to Example 1 , using 7-ethylindole instead of 7-chloroindole, was dissolved in dry dichloromethane (1 ml) in a 5 ml microwave vial and potassium carbonate was added (70 mg, 0.51 mmol) followed by Lambda/-methyl glycine amide hydrochloride (26 mg, 0.21 mmol). The mixture is heated in a microwave oven at 100 0C for 3 mins. After cooling down to room temperature, the mixture was partitioned between water and dichloromethane. The organic phase was separated, washed with water, dried over magnesium sulfate and evaporated in vacuo. The crude oil was prepurified on a 2 g SCX column and on a 2 g Si-based lsolute column eluting with 50%-100% (v/v) ethyl acetate in n-heptane. The free base was converted into its hydrochloride salt by dissolving it in dry dichloromethane and adding a 2M solution of HCI in ether to afford the title compound: (7.9 mg, 0.017 mmol). EsIMS: m/z 428.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 9 7-Ethyl-3-[(5-[N-(carboxamido)methyl]-N-methylamino}methyl)-([1,2,4]-thiadiazol-3-yl)]-1-(tetrahydropyran-4-yl)methyl-1H-indole, hydrochloride acid salt Methanesulfonic acid 3-(1-tetrahydropyran-4-yl)methyl-7-ethyl-1H-indol-3-yl)-([1,2,4]thiadiazol-5-ylmethyl ester (30 mg, 0.07 mmol) prepared according to Example 1, using 7-ethylindole instead of 7-chloroindole, was dissolved in dry dichloromethane (1 ml) in a 5 ml microwave vial and potassium carbonate was added (70 mg, 0.51 mmol) followed by N-methyl glycine amide hydrochloride (26 mg, 0.21 mmol). The mixture is heated in a microwave oven at 100 C. for 3 mins. After cooling down to room temperature, the mixture was partitioned between water and dichloromethane. The organic phase was separated, washed with water, dried over magnesium sulfate and evaporated in vacuo. The crude oil was prepurified on a 2 g SCX column and on a 2 g Si-based Isolute column eluding with 50%-100% (v/v) ethyl acetate in n-heptane. The free base was converted into its hydrochloride salt by dissolving it in dry dichloromethane and adding a 2M solution of HCl in ether to afford the title compound: (7.9 mg, 0.017 mmol). EsIMS: m/z 428.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 20 7-Chloro-3-[(5-[N-(carboxamido)methyl]-N-methylamino]methyl)-([1,2,4]oxadiazol-3-yl)]-1-(tetrahydropyran-4-yl)methyl-1H-indole, hydrochloride salt To a solution of 7-chloro-3-[(5-chloromethyl)-([1,2,4]oxadiazol-3-yl)]-1-(tetrahydropyran-4-yl)methyl-1H-indole (Example 19; Step C; 1.5 g, 4.09 mmol) in 1-methyl-2-pyrrolidinone (5 ml) was added N-methyl glycine amide hydrochloride (1.0 g, 8.19 mmol) and potassium carbonate (3.4 g, 24.6 mmol). The reaction was stirred at room temperature for 18 h before being diluted with dichloromethane (10 ml) and filtered through a 20 g Strata SCX giga tube. The tube was washed with methanol and then eluted with 2 M ammonia in methanol. The methanolic ammonia solution was evaporated to dryness. This was re-dissolved in dichloromethane, washed with water and brine, dried over sodium sulfate and the solvent removed in vacuo. The resulting residue was purified by flash column chromatography eluding with 2% (v/v) ethanol in dichloromethane. The solid was dissolved in dichloromethane and hydrogen chloride (2M solution in diethyl ether) was added. The resultant hydrochloride salt was crystallized from acetone to afford the title compound as a 1:1 hydrochloride salt (1.24 g, 2.73 mmol). EsIMS: m/z 418.3 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 5 7-Methoxy-3-[(5-[(N-carboxamido)methyl]methylamino}methyl)-([1,2,4]-thiadiazol-3-yl)]-1-(tetrahydropyran-4-yl) methyl-1H-indole, trifluoroacetic acid salt Methanesulfonic acid 3-(1-tetrahydropyran-4-yl)methyl-7-methoxy-indol-3-yl)-([1,2,4]thiadiazol-5-ylmethyl ester (106 mg, 0.25 mmol), prepared according to the method of Example 1 using 7-methoxyindole instead of 7-chloroindole, was dissolved in acetonitrile (2 ml) and transferred into a microwave vial. N-methyl glycine amide hydrochloride (53 mg, 1.26 mmol) and potassium carbonate (174 mg, 1.26 mmol) were added and the reaction mixture subjected to microwave irradiation at 150 C. for 30 mins using an Emrys Optimizer EXP. The free base was purified by semi-prep. HPLC (Method i) to afford the title compound as a 1:1 trifluoroacetic acid salt (17.4 mg, 0.03 mmol). EsIMS: m/z 452.1 [M+Na]+, 429.8 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10% | With sodium tris(acetoxy)borohydride; acetic acid; In tetrahydrofuran; at 60℃; for 16h; | A solution of Intermediate 13A (50 mg, 148 muiotaetaomicron) in THF (2 ml) was treated with N-methyl- glycinamide hydrochloride (92 mg, 739 muiotaetaomicron), sodium triacetoxyborohydride (157 mg, 739 muiotaetaomicron) and acetic acid (17 mu, 296 muiotaetaomicron), and the mixture was stirred at 60C for 16 h. After this, the reaction mixture was directly separated by preparative RP-HPLC (Reprosil CI 8, gradient 20-40% acetonitrile/0.2%) aq. TFA). The product fractions were combined and evaporated to dryness, and the residue was dissolved in methanol and filtered through an anion exchange cartridge (StratoSpheres SPE, PL-HCO3 MP -resin). The cartridge was eluted with methanol, and the filtrate was evaporated yielding 7 mg (10%> of th.) of the title compound. LC-MS (method 4): Rt = 0.58 min; MS (ESIpos): m/z = 411 (M+H)+ -NMR (400 MHz, DMSO-de): inter al. delta = 7.91 (s, 1H), 7.9 (br. s, 1H), 7.83 (s, 1H), 7.60-7.66 (m, 1H), 7.35 (s, 1H), 7.30 (s, 1H), 6.84 (s, 1H), 5.7 (br. s, 1H), 3.95 (s, 3H), 3.65 (d, 2H), 3.04 (d, 2H), 2.45 (s, 3H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | With sodium tris(acetoxy)borohydride; acetic acid; In tetrahydrofuran; at 60℃; for 16h; | A solution of Intermediate 13A (48 mg, 142 muiotaetaomicron) in THF (2 ml) was treated with N2-methyl- glycinamide hydrochloride (88 mg, 709 muiotaetaomicron), sodium triacetoxyborohydride (150 mg, 709 muiotaetaomicron) and acetic acid (16 mu, 284 muiotaetaomicron), and the mixture was stirred at 60C for 16 h. After this, the reaction mixture was directly separated by preparative RP-HPLC (Reprosil CI 8, gradient 30-50% acetonitrile/0.2%) aq. formic acid). The product fractions were combined, neutralized with 1 M aq. ammonia and concentrated under vacuum. The remaining aqueous solution was diluted 1 : 1 with 1 ,4- dioxane and lyophilized. The product thus obtained was dissolved in ethyl acetate and washed with brine. The organic layer was dried with magnesium sulfate, filtered and evaporated to dryness. The residue was purified by preparative TLC (silica gel, dichloromethane/7 M ammonia in methanol 20:1) yielding 4 mg (6%> of th.) of the title compound. LC-MS (method 4): Rt = 0.58 min; MS (ESIpos): m/z = 411 (M+H)+ -NMR (400 MHz, DMSO-de): delta = 7.92-7.94 (m, 2H), 7.36 (s, 1H), 7.30 (s, 1H), 7.09-7.14 (m, 1H), 7.04-7.09 (m, 1H), 6.84 (s, 1H), 5.7 (br. s, 1H), 3.94-3.96 (m, 5H), 3.57 (s, 2H), 2.83 (s, 2H), 2.45 (s, 3H), 2.15 (s, 3H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.00 mg | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 17.5h; | General procedure: Example 23 N-(2-amino-2-oxoethyl)-N, 4-dimethyl-1-[2-methyl-4-(3-methyl-1H-pyrazol-1-yl)benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepine-4-carboxamide (racemate) 4-methyl-1-[2-methyl-4-(3-methyl-1H-pyrazol-1-yl)benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepine-4-carboxylic acid (racemate: 20.0 mg) was dissolved into methylene chloride (1.5 mL), thereto were added 1-hydroxybenzotriazole (13.4 mg), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (19.0 mg), and <strong>[5325-64-4]N-methylglycinamide hydrochloride</strong> (12.4 mg), and the reaction mixture was stirred at room temperature for 17.5 hours. After the reaction solution was added with water and extracted with methylene chloride, the organic phase was washed with an aqueous saturated sodium hydrogen carbonate solution and saturated saline in sequence, and then dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated with a reduced pressure, and the obtained residue was purified by thin layer silica gel chromatography (chloroform/methanol=10/1) to thus obtain the title compound (2.00 mg) as a white solid. 1H-NMR (400 MHz, CDCl3) delta7.84-7.44 (m, 2H), 7.19-6.76 (m, 4H), 7.11 (dd, J=8.2, 2.0 Hz, 1H), 6.60 (d, J=7.4 Hz, 1H), 6.27-6.19 (m, 1H), 5.56 (brs, 1H), 5.33 (brs, 1H), 4.96-4.82 (m, 1H), 4.56-4.49 (m, 1H), 4.18-3.94 (m, 2H), 3.61-3.15 (m, 5H), 2.93-2.88 (m, 1H), 2.52-2.33 (m, 6H), 1.95-1.89 (m, 1H), 1.56 (brs, 2H), 1.26 (brs, 1H). ESI/MS (m/z) 474 (M+H)+, 472 (M-H)-. |
2 mg | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 17.5h; | 4-Methyl-1-[2-methyl-4-(3-methyl-1H-pyrazol-1-yl)benzylidene]-2,3,4,5-tetrahydro-1H- Benzo[b]azepine-4-carboxylic acid (racemic: 20.0 mg) was dissolved in dichloromethane (1.5 mL).Add 1-hydroxybenzotriazole (13.4 mg),1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (19.0 mg), and N-methylglycineamine hydrochloride (12.4 mg),Stir at room temperature for 17.5 hours. After adding water and extracting with dichloromethane, the organic phase was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine, and dried over anhydrous sodium sulfate.After filtration, the filtrate was concentrated under reduced pressure.Using thin layer gelatin chromatography (chloroform / methanol = 10/1)Purifying the residue obtained,The title compound (2.00 mg) was obtained as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With 4-methyl-morpholine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; In N,N-dimethyl-formamide; at 20℃; for 16h;Cooling with ice; | [1238] N-methylmorpholine (0.107 mL, 0.986 mmol),TBTU (0.191 g, 0.592 mmol) and 2-(methylamino)acetamidehydrochloride (0.123 g, 0.986 mmol) were added to anice-cooled suspension of331e) (0.2 g, 0.493 mmol) in DMF( 4 mL ). The reaction mixture was stirred at room temperaturefor 16 h and then diluted with ice-cold water. A precipitatewas filtered off and dissolved in dichloromethane. Theorganic phase was washed with sodium hydrogen carbonatesolution (20 mL) and brine (20 mL ), dried over sodium sulfateand evaporated. The renmant was purified by flash columnchromatography [silica gel; dichloromethane with 4% methano]followed by preparative HPLC. White solid. Yield: 65 mg(28% of theory)[1239] HPLC-MS (method 5): R,=3.13 min; m/z [M+Ht=476.2[1240] 1H NMR (400 MHz, DMSO-d6, 100 C., o ppm):9.05 (s, 2H), 8.86 (s, lH), 8.26 (s, lH), 7.81 (d, lH, 1=8.0 Hz),7.56 (d, lH, 1=7.6 Hz), 7.32-7.24 (m, 3H), 6.92 (bs, 2H),5.13-5.1 (m, lH), 4.88 (bs, lH), 4.0 (s, 2H), 3.03 (s, 3H),2.74-2.69 (m, 2H), 1.58 (d, 3H, 1=6.0 Hz), 1.27 (t, 3H, 1=7.2Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | To a suspension of 2,6-dichloro-4-ethylpyridine-3,5-dicarbonitrile (synthesis described in example 3, step 2, 1.7 g, 7.52 mmol) in ethanol (30 mL) mechanically stirring at -20 C was added a solution of 2-(methylamino)acetamide, Hydrochloride (1.0 g, 8.03 mmol) and Et3N (2.17 mL, 15.57 mmol) in ethanol (30 mL). The reaction mixture was then stirred at -20 C for 45 minutes. To the reaction mixture was then added potassium ethanethioate (1.3 g, 11.38 mmol) and Et3N (2.62 mL, 18.80 mmol). The heterogeneous reaction mixture was then warmed to 40 C and stirred at the same temperature. After stirring overnight at 40 C, the reaction mixture was cooled to room temperature. To the room temperature reaction mixture was added 2-amino-2-oxo-1-phenylethyl methanesulfonate (synthesis described in example 3, step 5, 2.6 g, 11.34 mmol). The reaction was warmed to 40 C and stirred at the same temperature for 3.5 hours. The reaction mixture cooled to 20 C and then was filtered. The solid was then washed with 300 mL of EtOH, followed by 300 mL of water. The resulting white solid was then again washed with EtOH (200 mL) followed by 100 mL of Et2O. The solid was then dried in the vacuum oven overnight to obtain 2-((6-((2-amino-2- oxoethyl)(methyl)amino)-3,5-dicyano-4-ethylpyridin-2-yl)thio)-2-phenylacetamide (1.53 g, 3.75 mmol, 50% yield) as a white solid. LCMS m/z = 409.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) delta ppm 7.83 (s, 1H), 7.62 (s, 1H), 7.47-7.53 (m, 2H), 7.32-7.42 (m, 5H), 5.59 (s, 1H), 4.52 (d, J=17.49 Hz, 1H), 4.29 (d, J=17.24 Hz, 1H), 3.39 (s, 3H), 2.77 (q, J=7.60 Hz, 2H), 1.21 (t, J=7.48 Hz, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32 g | With triethylamine; In dichloromethane; at 20℃; for 1h; | To a stirred solution of 2-(methylamin (20.41 g, 164 mmol) in dichloromethane (1000 mL) was added triethylamine (54.6 mL, 378 mmol) followed by 2,6- dichloro-4-cyclopropylpyridine-3,5-dicarbonitrile (synthesis described in example 4 step 2, 30 g, 126 mmol). The reaction mixture was stirred at room temperature for 1 hour. Water (1000 mL) was added and the mixture extracted with DCM (2 x 1000 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to obtain the crude material. Purification of the crude material by silica gel chromatography (60-120 mesh; 10% MeOH/EtOAc as eluent) afforded 2-((6-chloro-3,5-dicyano-4- cyclopropylpyridin-2-yl)(methyl)amino)acetamide (32 g). LCMS m/z = 290.4 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | A solution of 2-(5-{1 -[(6,7-dimethoxy-2-methylquinazolin-4-yl)amino]ethyl}thiophen-2- yl)benzaldehyde (described in example 179a; 50.0 mg, 1 15 muetaetaomicronIota) and <strong>[5325-64-4]N-methylglycinamide hydrochloride</strong> (1 :1) (14.4 mg, 1 15 muetaetaomicronIota) in MeOH (1.2 mL) was stirred at room temperature during 5 hours. NaBH(OAc)3 (48.9 mg, 231 muetaetaomicronIota) was added and the solution stirred at room temperature during 15mn. The reaction was quenched with aqueous NaOH (1.0 M, 1.0 mL), the mixture extracted with DCM and the solvent removed in vacuo. Purification by column chromatography (silica gel, MeOH/EtOAc 0-50% then MeOH) followed by preparative HPLC (basic conditions) gave the title compound as a white solid (26.0 mg, 45%). 1H-NMR (400 MHz, DMSO-de): delta [ppm] = 8.15 (d, 1H), 7.67 (br d, 1H), 7.64 (s, 1H), 7.55 (d, 1H), 7.35-7.29 (m, 2H), 7.29-7.24 (m, 1H), 7.10 (d, 1H), 7.08 (dd, 1H), 7.05 (s, 1H), 5.96 (quin, 1H), 3.87 (s, 6H), 3.70 (s, 2H), 3.04 (s, 2H), 2.56 (d, 3H), 2.43 (s, 3H), 1.71 (d, 3H). LC-MS (method 7): m/z: [M+H]+ = 506, Rt = 0.56 min. |
Tags: 5325-64-4 synthesis path| 5325-64-4 SDS| 5325-64-4 COA| 5325-64-4 purity| 5325-64-4 application| 5325-64-4 NMR| 5325-64-4 COA| 5325-64-4 structure
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
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. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
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.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :
Total Compounds: mg
The concentration of the dissolution solution you need to prepare is mg/mL