Structure of 121010-86-4
*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
*For Research Use Only !
Change View
Size | Price | VIP Price | US Stock |
Global Stock |
In Stock | ||
{[ item.pr_size ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | Inquiry {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock 1-2 weeks - Inquiry - | Login | - + | Inquiry |
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
1-2weeks
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
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. : | 121010-86-4 |
Formula : | C4H8N2O |
M.W : | 100.12 |
SMILES Code : | O=C1NCC[C@H]1N |
MDL No. : | MFCD11501145 |
InChI Key : | YNDAMDVOGKACTP-GSVOUGTGSA-N |
Pubchem ID : | 21969418 |
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 | 0.75 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 28.85 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.78 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-1.2 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.08 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.65 |
Log S (ESOL):? ESOL: Topological method implemented from |
0.3 |
Solubility | 198.0 mg/ml ; 1.97 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.54 |
Solubility | 344.0 mg/ml ; 3.44 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.26 |
Solubility | 54.9 mg/ml ; 0.548 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 |
-7.76 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) |
1.38 |
* 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 triethylamine; In methanol; at 20℃;Reflux; | To a solution of (R) -aminopyrrolidin-2-one (1.7 g) and triethylamine (4.73 mL) in methanol (20 mL) was added di-tert- butyl bicarbonate (5.91 mL) . The reaction mixture was stirred at room temperature overnight and further heated under reflux for 2 hr. The reaction mixture was concentrated, and the residue was purified by silica gel column chromatography(ethyl acetate) .XH NMR (300 MHz, DMSO-d6) delta 1.38 (9H, s) , 1.70-1.93 (1H, m) , 2.11-2.35 (1H, m) , 3.12 (2H, dd, J = 9.3, 5.0 Hz), 3.88-4.11 (1H, m) , 7.00 (1H, d, J = 8.7 Hz), 7.69 (1H, s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Example 106 4-Amino-6-(ethoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-N-[(3R)-2-oxopyrrolidin-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide A stirred solution of Intermediate 64A (50 mg, 121 mumol) in DMF (2 ml) was treated at rt with N-[(1H-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium tetrafluoroborate (TBTU) (43 mg, 133 mumol) and DIPEA (53 mul, 303 mumol). After 15 min, <strong>[121010-86-4](3R)-3-aminopyrrolidin-2-one</strong> (24 mg, 242 mumol) was added, and the resulting mixture was stirred at rt for further 2 h. After this, the mixture was separated by preparative RP-HPLC (Reprosil C18, gradient 30-50% acetonitrile/0.2% aq. trifluoroacetic acid). The product fractions were combined and evaporated to dryness. 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 affording 36 mg (60% of th.) of the title compound. LC-MS (method 2): Rt=0.91 min; MS (ESIpos): m/z=495 (M+H)+ 1H-NMR (400 MHz, DMSO-d6): delta=9.50 (d, 1H), 8.21-8.45 (br. s, 1H), 8.17 (s, 1H), 7.97 (s, 1H), 7.41 (s, 1H), 7.33 (s, 1H), 6.86 (s, 1H), 5.84-6.09 (br. s, 1H), 4.74 (dd, 2H), 4.47-4.56 (m, 1H), 3.96 (s, 3H), 3.37 (q, 2H), 3.22-3.29 (m, 2H), 2.54-2.61 (m, 1H), 2.46 (s, 3H), 1.90-2.03 (m, 1H), 1.00 (t, 3H) ppm. | |
60% | A stirred solution of Intermediate 64A (50 mg, 121 muiotaetaomicron) in DMF (2 ml) was treated at rt with N-[(lH-benzotriazol-l-yloxy)(dimethylamino)methylene]-N-methylmethanaminium tetrafluoroborate (TBTU) (43 mg, 133 muiotaetaomicron) and DIPEA (53 mu, 303 muetaiotaomicron). After 15 min, (3R)-3-aminopyrrolidin-2- one (24 mg, 242 muiotaetaomicron) was added, and the resulting mixture was stirred at rt for further 2 h. After this, the mixture was separated by preparative RP-HPLC (Reprosil CI 8, gradient 30-50% acetonitrile/0.2%) aq. trifluoroacetic acid). The product fractions were combined and evaporated to dryness. 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 affording 36 mg (60% of th.) of the title compound. LC-MS (method 2): Rt = 0.91 min; MS (ESIpos): m/z = 495 (M+H)+ -NMR (400 MHz, DMSO-de): delta = 9.50 (d, 1H), 8.21-8.45 (br. s, 1H), 8.17 (s, 1H), 7.97 (s, 1H), 7.41 (s, 1H), 7.33 (s, 1H), 6.86 (s, 1H), 5.84-6.09 (br. s, 1H), 4.74 (dd, 2H), 4.47-4.56 (m, 1H), 3.96 (s, 3H), 3.37 (q, 2H), 3.22-3.29 (m, 2H), 2.54-2.61 (m, 1H), 2.46 (s, 3H), 1.90-2.03 (m, 1H), 1.00 (t, 3H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | Example 3 (3R)-3-([4-Amino-6-(methoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo-[2,1-f][1,2,4]triazin-7-yl]methyl}amino)pyrrolidin-2-one dihydrochloride A solution of Intermediate 13A (520 mg, 1.36 mmol) in methanol (15 ml) and acetic acid (156 mul, 2.7 mmol) was treated with <strong>[121010-86-4](R)-3-aminopyrrolidin-2-one</strong> (503 mg, 5.0 mmol) and triacetoxyborohydride (1.06 g, 5.0 mmol). The mixture was stirred at rt overnight and then evaporated. Purification by preparative RP-HPLC (Reprosil C18, gradient 10-95% acetonitrile/0.1% aq. formic acid) and lyophilization of the product thus obtained from a 4 M solution of hydrogen chloride in 1,4-dioxane afforded 272 mg (36% of th.) of the title compound. LC-MS (method 2): Rt=0.70 min; MS (ESIpos): m/z=467 (M+H)+ [0691] 1H-NMR (400 MHz, DMSO-d6): delta=9.62 (br. s, 1H), 9.46 (br. s, 1H), 8.56-8.22 (br. s, 1H), 8.44 (s, 1H), 8.19 (s, 1H), 7.38 (s, 1H), 7.34 (s, 1H), 6.87 (s, 1H), 6.54-6.12 (br. s, 1H), 4.89-4.65 (m, 2H), 4.58-4.46 (m, 2H), 4.17-4.07 (br. s, 1H, overlap with water peak), 3.96 (s, 3H), 3.36-3.16 (m, 2H), 3.25 (s, 3H), 2.48-2.39 (m, 1H), 2.46 (s, 3H), 2.23-2.06 (m, 1H) ppm | |
36% | A solution of Intermediate 13A (520 mg, 1.36 mmol) in methanol (15 ml) and acetic acid (156 mu, 2.7 mmol) was treated with <strong>[121010-86-4](R)-3-aminopyrrolidin-2-one</strong> (503 mg, 5.0 mmol) and triacetoxyboro- hydride (1.06 g, 5.0 mmol). The mixture was stirred at rt overnight and then evaporated. Purification by preparative RP-HPLC (Reprosil C18, gradient 10-95% acetonitrile/0.1%> aq. formic acid) and lyophilization of the product thus obtained from a 4 M solution of hydrogen chloride in 1,4-dioxane afforded 272 mg (36% of th.) of the title compound. LC-MS (method 2): Rt = 0.70 min; MS (ESIpos): m/z = 467 (M+H)+ -NMR (400 MHz, DMSO-de): d = 9.62 (br. s, 1H), 9.46 (br. s, 1H), 8.56-8.22 (br. s, 1H), 8.44 (s, 1H), 8.19 (s, 1H), 7.38 (s, 1H), 7.34 (s, 1H), 6.87 (s, 1H), 6.54-6.12 (br. s, 1H), 4.89-4.65 (m, 2H), 4.58-4.46 (m, 2H), 4.17-4.07 (br. s, 1H, overlap with water peak), 3.96 (s, 3H), 3.36-3.16 (m, 2H), 3.25 (s, 3H), 2.48-2.39 (m, 1H), 2.46 (s, 3H), 2.23-2.06 (m, 1H) ppm |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With sodium tris(acetoxy)borohydride; acetic acid; In methanol; at 20℃; | Example 4 (3R)-3-([4-Amino-6-(methoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo-[2,1-f][1,2,4]triazin-7-yl]methyl}amino)pyrrolidin-2-one A solution of Intermediate 13A (2.0 g, 5.2 mmol) in methanol (58 ml) and acetic acid (0.6 ml) was treated with <strong>[121010-86-4](R)-3-aminopyrrolidin-2-one</strong> (785 mg, 7.8 mmol) and triacetoxyborohydride (3.32 g, 15.6 mmol). The mixture was stirred at rt overnight. After this, the reaction mixture was diluted with sat. aq. sodium hydrogencarbonate solution and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated. The residue was purified by two-fold column chromatography on silica gel (dichloromethane/methanol 40:1 to 10:1) to afford 957 mg (37% of th.) of the title compound. LC-MS (method 4): Rt=0.72 min; MS (ESIpos): m/z=467 (M+H)+ 1H-NMR (400 MHz, DMSO-d6): delta=8.01 (s, 1H), 7.75 (s, 1H), 7.35 (s, 1H), 7.31 (s, 1H), 6.85 (s, 1H), 4.46-4.34 (m, 2H), 4.24-4.02 (m, 2H), 3.96 (s, 3H), 3.24-3.04 (m, 3H), 3.21 (s, 3H), 2.45 (s, 3H), 2.40-2.27 (m, 1H), 1.80-1.65 (m, 1H) ppm. |
37% | With sodium tris(acetoxy)borohydride; acetic acid; In methanol; at 20℃; | A solution of Intermediate 13A (2.0 g, 5.2 mmol) in methanol (58 ml) and acetic acid (0.6 ml) was treated with <strong>[121010-86-4](R)-3-aminopyrrolidin-2-one</strong> (785 mg, 7.8 mmol) and triacetoxyborohydride (3.32 g, 15.6 mmol). The mixture was stirred at rt overnight. After this, the reaction mixture was diluted with sat. aq. sodium hydrogencarbonate solution and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated. The residue was purified by two-fold column chromatography on silica gel (dichloromethane/methanol 40:1 to 10:1) to afford 957 mg (37% of th.) of the title compound. LC-MS (method 4): Rt = 0.72 min; MS (ESIpos): m/z = 467 (M+H)+ 'H-NMR (400 MHz, DMSO-de): delta = 8.01 (s, 1H), 7.75 (s, 1H), 7.35 (s, 1H), 7.31 (s, 1H), 6.85 ( 1H), 4.46-4.34 (m, 2H), 4.24-4.02 (m, 2H), 3.96 (s, 3H), 3.24-3.04 (m, 3H), 3.21 (s, 3H), 2.45 ( 3H), 2.40-2.27 (m, 1H), 1.80-1.65 (m, 1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With sodium tris(acetoxy)borohydride; acetic acid; In tetrahydrofuran; at 20℃; for 3h; | A suspension of Intermediate 13A (100 mg, 0.233 mmol) in THF (2 ml) was treated with (S)-3- aminopyrrolidin-2-one (35 mg, 0.349 mmol), sodium triacetoxyborohydride (148 mg, 0.698 mmol) and acetic acid (26.6 mu, 0.465 mmol). The resulting mixture was stirred at rt for 3 h and then directly purified by preparative RP-HPLC (Reprosil CI 8, gradient 40-60% acetonitrile/0.2% aq. trifluoroacetic acid). The product fractions were combined and evaporated to dryness. 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 affording 56 mg (51% of th.) of the title compound. LC-MS (method 4): Rt = 0.72 min; MS (ESIpos): m/z = 467 (M+H)+ -NMR (400 MHz, DMSO-de): delta = 8.01 (s, 1H), 7.76 (s, 1H), 7.35 (s, 1H), 7.31 (s, 1H), 6.85 (s, 1H), 4.48 (d, 2H), 4.43 (d, 2H), 4.24-4.02 (m, 2H), 3.96 (s, 3H), 3.26-2.99 (m, 6H), 2.45 (s, 3H), 2.40-2.27 (m, 1 H), 1.82-1.64 (m, 1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46 mg | Example 7 (3R)-3-([4-Amino-6-(ethoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo-[2,1-f][1,2,4]triazin-7-yl]methyl}amino)pyrrolidin-2-one dihydrochloride A solution of Intermediate 17A (60 mg, purity 69%, 104 mumol) in methanol (3 ml) was treated with <strong>[121010-86-4](R)-3-aminopyrrolidin-2-one</strong> (22 mg, 209 mumol), sodium cyanoborohydride (33 mg, 522 mumol) and acetic acid (12 mul, 209 mumol). The mixture was stirred at 60 C. for 4 h and then filtered. The filtrate was purified by preparative RP-HPLC (Reprosil C18, gradient 40-60% acetonitrile/0.2% aq. TFA). The product fractions were combined, diluted with 1 M hydrochloric acid and evaporated to dryness yielding 46 mg (79% of th.) of the title compound. LC-MS (method 4): Rt=0.74 min; MS (ESIpos): m/z=481 (M+H)+ 1H-NMR (400 MHz, DMSO-d6): delta=9.58-9.75 (m, 1H), 9.33-9.54 (m, 1H), 8.44 (s, 1H), 8.27-8.71 (br. s, 1H), 8.19 (s, 1H), 7.38 (s, 1H), 7.34 (s, 1H), 6.87 (s, 1H), 6.18-6.48 (br. s, 1H), 4.68-4.87 (m, 2H), 4.49-4.62 (q, 2H), 3.96 (s, 3H), 3.45 (q, 2H), 3.18-3.35 (m, 2H), 2.46 (s, 4H), 2.08-2.22 (m, 1H), 1.10 (t, 3H) ppm. | |
46 mg | A solution of Intermediate 17A (60 mg, purity 69%, 104 muiotaetaomicron) in methanol (3 ml) was treated with <strong>[121010-86-4](R)-3-aminopyrrolidin-2-one</strong> (22 mg, 209 muiotaetaomicron), sodium cyanoborohydride (33 mg, 522 muiotaetaomicron) and acetic acid (12 mu, 209 muiotaetaomicron). The mixture was stirred at 60C for 4 h and then filtered. The filtrate was purified by preparative RP-HPLC (Reprosil CI 8, gradient 40-60% acetonitrile/ 0.2%> aq. TFA). The product fractions were combined, diluted with 1 M hydrochloric acid and evaporated to dryness yielding 46 mg (79%> of th.) of the title compound. LC-MS (method 4): Rt = 0.74 min; MS (ESIpos): m/z = 481 (M+H)+ 'H-NMR (400 MHz, DMSO-de): delta = 9.58-9.75 (m, 1H), 9.33-9.54 (m, 1H), 8.44 (s, 1H), 8.27-8.71 (br. s, 1H), 8.19 (s, 1H), 7.38 (s, 1H), 7.34 (s, 1H), 6.87 (s, 1H), 6.18-6.48 (br. s, 1H), 4.68-4.87 (m, 2H), 4.49-4.62 (q, 2H), 3.96 (s, 3H), 3.45 (q, 2H), 3.18-3.35 (m, 2H), 2.46 (s, 4H), 2.08-2.22 (m, 1H), 1.10 (t, 3H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
180 mg | With sodium cyanoborohydride; acetic acid; In methanol; at 20℃; for 1.5h; | Example 8 (3R)-3-([4-Amino-6-(ethoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo-[2,1-f][1,2,4]triazin-7-yl]methyl}amino)pyrrolidin-2-one A solution of Intermediate 17A (226 mg, purity 75%, 428 mumol) in methanol (4 ml) was treated with <strong>[121010-86-4](R)-3-aminopyrrolidin-2-one</strong> (85 mg, 855 mumol), sodium cyanoborohydride (134 mg, 2.14 mmol) and acetic acid (49 mul, 855 mumol). The mixture was stirred at rt for 1.5 h. After this, the mixture was directly separated by preparative RP-HPLC (Reprosil C18, gradient 40-60% acetonitrile/0.2% aq. TFA). The product fractions were combined, diluted with sat. aq. sodium hydrogencarbonate solution and extracted with ethyl acetate. The combined organic phases were washed with sat. aq. sodium chloride solution, dried over magnesium sulfate and evaporated to dryness yielding 180 mg (88% of th.) of the title compound. LC-MS (method 4): Rt=0.74 min; MS (ESIpos): m/z=481 (M+H)+ 1H-NMR (400 MHz, DMSO-d6): delta=8.00 (s, 1H), 7.76 (s, 1H), 7.8-8.1 (br. s, 1H), 7.35 (s, 1H), 7.31 (s, 1H), 6.84 (s, 1H), 5.6-5.9 (br. s, 1H), 4.39-4.49 (m, 2H), 4.04-4.23 (m, 2H), 3.96 (s, 3H), 3.41 (q, 2H), 3.05-3.23 (m, 3H), 2.45 (s, 3H), 2.31-2.40 (m, 1H), 1.68-1.79 (m, 1H), 1.08 (t, 3H) ppm. |
180 mg | A solution of Intermediate 17A (226 mg, purity 75%, 428 muiotaetaomicron) in methanol (4 ml) was treated with <strong>[121010-86-4](R)-3-aminopyrrolidin-2-one</strong> (85 mg, 855 muiotaetaomicron), sodium cyanoborohydride (134 mg, 2.14 mmol) and acetic acid (49 mu, 855 muiotaetaomicron). The mixture was stirred at rt for 1.5 h. After this, the mixture was directly separated by preparative RP-HPLC (Reprosil CI 8, gradient 40-60% acetonitrile/0.2%> aq. TFA). The product fractions were combined, diluted with sat. aq. sodium hydrogencarbonate solution and extracted with ethyl acetate. The combined organic phases were washed with sat. aq. sodium chloride solution, dried over magnesium sulfate and evaporated to dryness yielding 180 mg (88%o of th.) of the title compound. LC-MS (method 4): Rt = 0.74 min; MS (ESIpos): m/z = 481 (M+H)+ 'H-NMR (400 MHz, DMSO-de): delta = 8.00 (s, 1H), 7.76 (s, 1H), 7.8-8.1 (br. s, 1H), 7.35 (s, 1H), 7.31 (s, 1H), 6.84 (s, 1H), 5.6-5.9 (br. s, 1H), 4.39-4.49 (m, 2H), 4.04-4.23 (m, 2H), 3.96 (s, 3H), 3.41 (q, 2H), 3.05-3.23 (m, 3H), 2.45 (s, 3H), 2.31-2.40 (m, 1H), 1.68-1.79 (m, 1H), 1.08 (t, 3H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With sodium cyanoborohydride; acetic acid; In methanol; at 60℃; for 16h; | Example 56 (3R)-3-[({7-[(4-Acetylpiperazin-1-yl)methyl]-4-amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-6-yl}methyl)amino]pyrrolidin-2-one A solution of Intermediate 31A (80 mg, 167 mumol) in methanol (1.4 ml) was treated with <strong>[121010-86-4](3R)-3-aminopyrrolidin-2-one</strong> (21 mg, 251 mumol), sodium cyanoborohydride (52 mg, 836 mumol) and acetic acid (19 mul, 334 mumol). After stirring at 60 C. for 16 h, the resulting mixture was separated by preparative RP-HPLC (Reprosil C18, gradient 20-40% acetonitrile/0.2% aq. TFA). The product thus obtained 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 46 mg (49% of th.) of the title compound._LC-MS (method 2): Rt=0.70 min; MS (ESIpos): m/z=563 (M+H)+ [0903] 1H-NMR (400 MHz, DMSO-d6): delta=8.42 (s, 1H), 8.05 (s, 1H), 7.93-8.24 (br. s, 1H), 7.51 (s, 1H), 7.34 (s, 1H), 6.88 (s, 1H), 5.75-6.07 (br. s, 1H), 4.21-4.37 (m, 2H), 4.19 (s, 2H), 4.10 (t, 1H), 3.96 (s, 3H), 3.56-3.66 (m, 2H), 3.44-3.54 (m, 4H), 3.11-3.27 (m, 4H), 2.47 (s, 4H), 2.16-2.25 (m, 1H), 2.00 (s, 3H), 1.86-1.95 (m, 1H) ppm |
49% | With sodium cyanoborohydride; acetic acid; In methanol; at 60℃; for 16h; | A solution of Intermediate 31A (80 mg, 167 muiotaetaomicron) in methanol (1.4 ml) was treated with (3R)-3- aminopyrrolidin-2-one (21 mg, 251 muiotaetaomicron), sodium cyanoborohydride (52 mg, 836 muiotaetaomicron) and acetic acid (19 mu, 334 muiotaetaomicron). After stirring at 60C for 16 h, the resulting mixture was separated by pre- parative RP-HPLC (Reprosil CI 8, gradient 20-40% acetonitrile/0.2% aq. TFA). The product thus obtained 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 46 mg (49%> of th.) of the title compound. LC-MS (method 2): Rt = 0.70 min; MS (ESIpos): m/z = 563 (M+H)+ -NMR (400 MHz, DMSO-de): delta = 8.42 (s, 1H), 8.05 (s, 1 H), 7.93-8.24 (br. s, 1H), 7.51 (s, 1H), 7.34 (s, 1 H), 6.88 (s, 1H), 5.75-6.07 (br. s, 1H), 4.21 -4.37 (m, 2H), 4.19 (s, 2H), 4.10 (t, 1 H), 3.96 (s, 3H), 3.56-3.66 (m, 2H), 3.44-3.54 (m, 4H), 3.1 1 -3.27 (m, 4H), 2.47 (s, 4H), 2.16-2.25 (m, 1H), 2.00 (s, 3H), 1.86-1.95 (m, 1H) ppm |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium cyanoborohydride; acetic acid; In methanol; at 60℃; for 20h; | To a suspension of Intermediate 10A (200 mg, 591 muetaiotaomicron) in methanol (5 ml) was added acetic acid (68 mu, 1.18 mmol), <strong>[121010-86-4](R)-3-aminopyrrolidin-2-one</strong> (89 mg, 887 muetaiotaomicron) and sodium cyanoborohydride (185 mg, 2.96 mmol). The mixture was stirred at 60C for 20 h and then directly purified by pre- parative RP-HPLC (Reprosil CI 8, gradient acetonitrile/0.2% aq. TFA). The product fractions were combined, diluted with 1 M hydrochloric acid and then evaporated yielding 228 mg (78% of th.) of the title compound. LC-MS (method 2): Rt = 0.73 min; MS (ESIpos): m/z = 423 (M+H)+ 1H-NMR (400 MHz, DMSO-d6): inter alia delta = 9.93-10.06 (br. s, 1H), 9.70-9.83 (br. s, 1H), 8.40- 8.80 (br. s, 1H), 8.43 (s, 1H), 8.20 (s, 1H), 7.39 (s, 1H), 7.32 (s, 1H), 7.17 (s, 1H), 6.85 (s, 1H), 6.56-7.24 (br. s, 1H), 4.79 (d, 1H), 4.60 (d, 1H), 4.00-4.10 (m, 1H), 3.96 (s, 3H), 3.17-3.34 (m, 2H), 2.45 (s, 3H), 2.09-2.22 (m, 1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | A solution of Intermediate 15A (50 mg, 141 muetaiotaomicron) in DMF (2 ml) was treated with TBTU (50 mg, 155 muetaiotaomicron) and DIPEA (61 mu, 353 muetaiotaomicron) and stirred at rt for 15 min. (JR)-3-Aminopyrrolidin-2- one (28 mg, 282 muetaiotaomicron) was added, and the resulting mixture was stirred at rt for 16 h. After this, the mixture was directly purified by preparative RP-HPLC (Reprosil CI 8, gradient acetonitrile/ 0.2% aq. TFA). The product fractions were combined, diluted with 1 M hydrochloric acid and evaporated affording 34 mg (50% of th.) of the title compound. LC-MS (method 2): Rt = 0.85 min; MS (ESIpos): m/z = 437 (M+H)+ 1H-NMR (400 MHz, DMSO-d6): inter alia delta = 9.21-9.28 (m, 1H), 8.58 (br. s, 1H), 8.24 (s, 1H), 8.02 (s, 1H), 7.42 (s, 1H), 7.28-7.35 (m, 2H), 6.84 (s, 1H), 3.96 (s, 3H), 3.23-3.31 (m, 2H), 2.45 (s, 3H), 1.90-2.05 (m, 1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | (Example 7) 4-(5-{(1R)-1-[4-(cyclopropylcarbonyl)phenoxy]propyl}-1,2,4-oxadiazol-3-yl)-2-fluoro-N-[(3R)-2-oxopyrrolidin-3-yl]benzamide 1-Hydroxybenzotriazole monohydrate (129 mg, 0.840 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (242 mg, 1.26 mmol) were added to an N,N-dimethylformamide (4 mL) solution of the compound obtained in Reference Example 8 (345 mg, 0.840 mmol) at room temperature. The mixture was stirred at the same temperature for 30 minutes. Subsequently, <strong>[121010-86-4](3R)-3-aminopyrrolidin-2-one</strong> (101 mg, 1.01 mmol) was added, and the mixture was further stirred at the same temperature for 30 minutes. Water and a saturated aqueous solution of sodium hydrogen carbonate were added to the reaction mixture, and the mixture was subjected to extraction five times with ethyl acetate. The organic layer thus obtained was washed with a 10% aqueous solution of sodium chloride, and then was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (ethyl acetate:methanol = 100:0 ? 90:10, v/v) to give the title compound (285 mg, yield: 69%). 1H-NMR (400 MHz, CDCl3) delta ppm: 8.21 (1H, t, J = 8 Hz), 8.03-7.96 (3H, m), 7.87 (1H, dd, J = 12, 1 Hz), 7.34-7.27 (1H, m), 7.04 (2H, d, J = 9 Hz), 5.98-5.90 (1H, m), 5.53 (1H, t, J = 6 Hz), 4.62-4.55 (1H, m), 3.50-3.45 (2H, m), 2.97-2.89 (1H, m), 2.63-2.57 (1H, m), 2.35-2.19 (2H, m), 2.18-2.05 (1H, m), 1.23-1.17 (2H, m), 1.14 (3H, t, J = 7 Hz), 1.04-0.97 (2H, m); MS (ESI) m/z: 493 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3% | (Example 10) 4-(5-{(1R)-1-[4-(cyclopropylcarbonyl)phenoxy]ethyl}-1,2,4-oxadiazol-3-yl)-2-fluoro-N-[(3R)-2-oxopyrrolidin-3-yl]benzamide 1-Hydroxybenzotriazole monohydrate (137 mg, 0.896 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (258 mg, 1.34 mmol) were added to an N,N-dimethylformamide (4 mL) solution of the compound obtained in Reference Example 11 (355 mg, 0.896 mmol) at room temperature. The mixture was stirred at the same temperature for 30 minutes. Subsequently, <strong>[121010-86-4](3R)-3-aminopyrrolidin-2-one</strong> (108 mg, 1.07 mmol) was added, and the mixture was further stirred at the same temperature for 30 minutes. Water was added to the reaction mixture, and the mixture was subjected to extraction five times with ethyl acetate. The organic layer thus obtained was washed with a saturated aqueous solution of sodium hydrogen carbonate and a 10% aqueous solution of sodium chloride, and then was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (ethyl acetate:methanol = 100:0 ? 90:10, v/v) to give the title compound (14.3 mg, yield: 3%). 1H-NMR (400 MHz, CDCl3) delta ppm: 8.21 (1H, t, J = 8 Hz), 8.02-7.97 (3H, m), 7.87 (1H, dd, J = 12, 1 Hz), 7.34-7.30 (1H, m), 7.05 (2H, d, J = 9 Hz), 5.78-5.74 (2H, m), 4.62-4.54 (1H, m), 3.49-3.45 (2H, m), 2.98-2.89 (1H, m), 2.64-2.57 (1H, m), 2.17-2.07 (1H, m), 1.92 (3H, d, J = 7 Hz), 1.22-1.18 (2H, m), 1.03-0.97 (2H, m) ; MS (ESI) m/z: 479 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | A solution of 100 mg (0.15 mmol) of 5-{4-[(2S)-2-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]amino}-3-oxo-3-[4-(2H-tetrazol-5-yl)phenyl]amino}propyl]phenyl}-6-methylpyridin-2-carboxylic acid and 29.3 mg (0:29 mmol) of <strong>[121010-86-4]3-aminopyrolidin-2-one</strong> in 1.25 ml of dimethylformamide was added with 77 mu (0.44 mmol) Nu, Nu-diisopropylethylamine and 83.5 mg (0:22 mmol) of N -[(dimethylamino) (3H-[1,2 3]triazolo[4,5-b] pyridin-3-yloxy)methylidene]-N-methylmethanaminiumhexafluorophosphate and stirred at RT for 24h. The reaction mixture was filtered and the filtrate purified by preparative HPLC (eluent: acetonitrile/water with 0.1% TFA (gradient)) separate. 68 mg (48% d. Th.) Of the title compound were obtained |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | 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 tetrahydrofuran; at 20℃; for 16h; | A solution of 4 '- [(2S)-2- [(ira Ae 4- [(ieri-butoxycarbonyl) amino] methyl} cyclohexyl) - carbonyl] amino} -3- (l / i -indazol-6-ylamino) -3-oxopropyl] -2-methylbiphenyl-4-carboxylic acid (100 mg, 0:15 mmol) and (3R) -3-aminopyrrolidine-2-one (18.3 mg, 0:18 mmol) in THF (5 ml) was treated with N, N-diisopropylamine (0.03 mL, 0:18 mmol) and HATU (70 mg, 0:18 mmol) was added thereto.The reaction mixture was stirred at RT overnight (ca. 16 h).The solvent was removed on a rotary evaporator and the residue dissolved in water / acetonitrile solved.The solution was filtered through a Millipore filter, then purified by preparative HPLC (eluent: gradient of acetonitrile / water with 0.1% trifluoroacetic acid).This gave 93 mg (83% d. Th.) Of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Into a 500 mL 3-necked round-bottom under nitrogen, was placed 41.1 (5 g, 19.90 mmol, 1.00 equiv) in CH2C12 (200 mL). This was followed by the addition of triphosgene (2.36 g, 79.70 mmol, 0.40 equiv) and Et3N (6 g, 59.29 mmol, 3.00 equiv) at -15 D-20C. The resulting solution was stirred for 30 min at 0 C in a water/ice bath. Compound 26.2 (2 g, 19.98 mmol, 1.00 equiv) was added to this solution. The reaction was allowed to react, with stirring, for an additional 30 min at room temperature. The reaction was quenched by the addition of H4C1 (aq.). The resulting solution was extracted with CH2C12, and the organic layers were combined and concentrated under vacuum. The crude product was re- crystallized from petroleum ether/CH2Cl2 in the ratio of 1 : 1. The solid was dried in an oven under reduced pressure to provide 0.4 g (72%) of 42.2 as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Into a 500-mL 3-necked round-bottom under nitrogen, was placed 191.1 (5 g, 19.82 mmol, 1.00 equiv), CH2CI2 (150 mL), triphosgene (2.36 g, 0.40 equiv). This was followed by the addition of Et3N (8 g, 79.06 mmol, 4.00 equiv) at - 30 C. The mixture was stirred for 1 h at 0 C. To this was added <strong>[121010-86-4](3R)-3-aminopyrrolidin-2-one</strong> (1.98 g, 19.78 mmol, 1.00 equiv). The reaction was stirred for 1 h at room temperature, and then then quenched by the addition of 150 mL of H4CI (aq). The solids were collected by filtration and dried in an oven under reduced pressure to provide 4.0 g (53%) of 191.2 as a light yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With 1,1,1,3,3,3-hexamethyl-disilazane; In acetonitrile;Reflux; | Into a 1000 mL 3-necked round-bottom flask, 26.1 (25 g, 161.71 mmol, 1.00 equiv), CH3CN (500 mL), and HMDS (261 g, 1.62 mol, 10.00 equiv) were added. The resulting solution was heated to reflux overnight. The resulting mixture was concentrated under vacuum. The reaction was quenched by the addition of 500 mL of methanol. The resulting mixture was concentrated under vacuum. The residue was dissolved in 100 mL of chloroform. The crude product was re-crystallized from ether/CHCl3 in the ratio of 5/1 to provide 12.5 g (77%) of 26.2 as a yellow solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.4 g | at 20℃; for 3h; | Into a 250 mL 3-necked round-bottom flask, was placed a solution of 1.4 and 26.2 (2 g, 19.98 mmol, 1.01 equiv). The reaction was stirred for 3 h at room temperature. The reaction was quenched by the addition of 100 mL of H4C1 (aq) and extracted with 2 x 100 mL of ethyl acetate. The organic layers were combined and concentrated. The crude product was re-crystallized from petroleum ether/CH2Cl2 in the ratio of 3/1 to provide 4.4 g (59%) of 26.3 as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | General procedure: N,N-Diisopropylethylamine (3.0-4.0 eq) was added to 8-methoxyquinoline-3-carboxylic acid (1.0 eq) in solvent (dichloromethane, tetrahydrofuran,or N,N-dimethylformamide, 0.05 to 0.2 M) at room temperature. Then, 1-((dimethylamino)(dimethyliminio)methyl)-1H-[1,2,3]triazolo[4,5-b]pyridine 3-oxide hexafluorophosphate(V)(1.0-1.5 eq) was added and the reaction mixture was stirred for five minutes. Then, amine (1.0 - 2.0 eq) was added and the reaction mixture was stirred for one to sixteen hours. 10% Aqueous citric acid was added and the reaction mixture was extracted with dichloromethane, washed with saturated sodium bicarbonate, dried over magnesium sulfate, filtered,and concentrated. The resulting residue was purified by RP HPLC or silica gel chromatography to give the quinoline-3-carboxamide (1%-95% yield). |
A780238 [56440-28-9]
(S)-3-Amino-2-pyrrolidinone Hydrochloride
Similarity: 0.97
A400460 [5626-52-8]
5-Oxopyrrolidine-2-carboxamide
Similarity: 0.89
A416499 [26081-03-8]
(R)-3-Aminoazepan-2-one hydrochloride
Similarity: 0.89
A780238 [56440-28-9]
(S)-3-Amino-2-pyrrolidinone Hydrochloride
Similarity: 0.97
A400460 [5626-52-8]
5-Oxopyrrolidine-2-carboxamide
Similarity: 0.89
A416499 [26081-03-8]
(R)-3-Aminoazepan-2-one hydrochloride
Similarity: 0.89
A780238 [56440-28-9]
(S)-3-Amino-2-pyrrolidinone Hydrochloride
Similarity: 0.97
A400460 [5626-52-8]
5-Oxopyrrolidine-2-carboxamide
Similarity: 0.89
A721949 [131900-62-4]
(R)-N-(Pyrrolidin-3-yl)acetamide
Similarity: 0.79
A185753 [1246277-44-0]
(S)-N-(Pyrrolidin-3-yl)acetamide hydrochloride
Similarity: 0.77