Structure of 6850-38-0
*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! Not for Human Use. We Do Not Sell to Patients.
Change View
| Size | Price | VIP Price |
DE Stock US Stock |
Asia Stock Global Stock |
In Stock |
| {[ item.pr_size ]}{[ size_append_text(item.pr_size, proInfo.prAm, 'list') ]} |
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) ]} | {[ item.p_spot_brand_remark ]} 1-2 weeks {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.p_spot_brand_remark ]} 1-2 weeks {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock Inquiry - | Login - + |
Please Login or Create an Account to: See VIP prices and availability
Asia Stock: Ship in 3-5 business days
EU Stock: ship in 0-1 business day
Global Stock: ship in 7-10 days
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
{[ item.p_spot_brand_remark ]}
1-2weeks
Inquiry
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) ]}
{[ item.p_spot_brand_remark ]}
1-2weeks
Inquiry
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
Asia Stock: Ship in 3-5 business days
EU Stock: ship in 0-1 business day
Global Stock: ship in 7-10 days
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
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. : | 6850-38-0 |
| Formula : | C6H13NO |
| M.W : | 115.17 |
| SMILES Code : | OC1C(N)CCCC1 |
| English Name : | 2-Aminocyclohexanol |
| MDL No. : | MFCD00191368 |
| InChI Key : | PQMCFTMVQORYJC-UHFFFAOYSA-N |
| Pubchem ID : | 23286 |
| Num. heavy atoms | 8 |
| Num. arom. heavy atoms | 0 |
| Fraction Csp3 | 1.0 |
| Num. rotatable bonds | 0 |
| Num. H-bond acceptors | 2.0 |
| Num. H-bond donors | 2.0 |
| Molar Refractivity | 32.71 |
| TPSA ? Topological Polar Surface Area: Calculated from |
46.25 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.17 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.06 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.25 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.21 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.39 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.39 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-0.52 |
| Solubility | 35.1 mg/ml ; 0.305 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-0.46 |
| Solubility | 39.9 mg/ml ; 0.347 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.1 |
| Solubility | 92.3 mg/ml ; 0.802 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 |
-7.05 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.85 |
* 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 |
|---|---|---|
| Stage #1: 5-phenyl-cyclohexane-1,3-dione; 2-aminocyclohexanol In tetrahydrofuran for 12h; Heating / reflux; Stage #2: With 2,4,6-trimethylphenyl bromide; potassium carbonate In DMF (N,N-dimethyl-formamide) at 150℃; for 4h; | 5 Reference Example 5 A mixture of 5-phenylcyclohexane-1,3-dione (4.0 g), 2-aminocyclohexanol (3.2 g), molecular sieves 4A (24 g) and tetrahydrofuran (60 ml) was refluxed for 12 hours and cooled, and insoluble materials were filtered off. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in dimethylformamide (100 ml). To the solution were added 2-bromomesitylene (4.2 g), tetrakistriphenylphosphine palladium (0.6 g) and potassium carbonate (5.9 g), and the mixture was stirred at 150° C. for 4 hours and concentrated under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was washed with sodium hydrogen carbonate solution, water and saturated brine, dried with magnesium sulfate and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (EtOAc), and the resulting crystals were recrystallized from ethyl acetate-hexane to give colorless crystals of 2-phenyl-1,2,3,4,5,6,7,8-octahydrocarbazol-4-one (3.4 g). mp. 257-259° C. 1H-NMR(CDCl3) δ: 1.60-1.90 (4H, m), 2.26-2.82 (6H, m), 2.84-3.06 (2H, m), 3.40-3.60 (1H, m), 7.16-7.48 (5H, m), 8.07 (1H, br). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 60% | With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 20℃; for 18h; | 3.I General Procedure for Step I. A [1- [5-ARYL-6-ALKYL-THIENO] [2,3-d] pyrimidin-4-yl]-piperidin-4-one 10 (0.134 mmol) and [1-AMINO-2-ALKYL] (aryl) alcohol (0.134 mmol) were mixed in dry dichloromethane [(2ML)] and then treated with sodiumtriacetoxyborohydride (0.2 mmol) and acetic acid (0.134 [MMOL).] The mixture was stirred at room temperature under N2 atmosphere for 18h until the reactants were consumed as determined by TLC analysis. The reaction mixture was quenched by addition of IN [NAOH] and the product was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated to afford crude product. The crude product was subjected to column chromatography (2% [MEOH/DCM)] to yield the product [11.] Typical yields were from 60-80%. The specific compounds listed below were made by this procedure, e. g. 2-[1-(5-Phenyl-thieno [2,3-d] [PYRIMIDIN-4-YL)-PIPERIDIN-4-YLAMINO]-CYCLOHEXANOL] 2-[1-(6-Methyl-5-phenyl-thieno [2,3-d] pyrimidin-4-yl)-piperidin-4-ylamino]- cyclohexanol 1-[1-(6-Methyl-5-phenyl-thieno [2,3-d] [PYRIMIDIN-4-YL)-PIPERIDIN-4-YLAMINO]-] indan-2-ol 5-Methoxy-2- [{ [I- (5-PHENYL-THIENO [2,] 3-d] [PYRIMIDIN-4-YL)-PIPERIDIN-4-YLAMINO]-] [ METHYL}-PHENOL] [BIS- (2-FLUORO-BENZYL)- [1- (5-PHENYL-THIENO [2,] 3-d] [PYRIMIDIN-4-YL)-PIPERIDIN-4-YL]-] amine 1- [{1- [5- (4-BROMO-PHENYL)-THIENO] [2,3-d] [PYRIMIDIN-4-YL]-PIPERIDIN-4-YLAMINO}-] indan-2-ol [ 1- [1- (5-P-TOLYL-THIENO [2, 3-D] PYRIMIDIN-4-YL)-PIPERIDIN-4-YLAMINO]-INDAN-2-OL] [2-FLUORO-6-[1-(6-METHYL-5-PHENYL-THIENO] [2,3-d] pyrimidin-4-yl) -piperidin-4- [ YLAMINO]-METHYL}-PHENOL] [2-] ({1-[5-(4-Bromo-phenyl)-thieno [2, 3-d]pyrimidin-4-yl]-piperidin-4-ylamino}- methyl)-6-fluoro-phenol 2-Fluoro-6-[1-(5-p-tolyl-thieno [2,3-d] pyrimidin-4-yl)-piperidin-4-ylamino]- methyl}-phenol [1- [I- (5-PHENYL-THIENO] [2, [3-D] PYRIMIDIN-4-YL)-PIPERIDIN-4-YLAMINO]-INDAN-2-OL] [1- (4-FLUORO-PHENOXY)-3- [1- (5-PHENYL-THIENO] [2,3-d] [PYRIMIDIN-4-YL)-PIPERIDIN-4-] ylamino]-propan-2-ol [1-JL- (5-PHENYL-THIENO] [2, 3-d]pyrimidin-4-yl)-piperidin-4-ylamino]-3-(4- trifluoromethoxy-phenoxy)-propan-2-ol [No. 1-(3, ]4-Difluoro-phenoxy) -3- {1-[5-(4-fluoro-phenyl)-thieno [2,3-d] pyrimidin-4- [ YL]-PIPERIDIN-4-YLAMINO}-PROPAN-2-OL] |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: 6-chloro-3-(2-methoxy-pyridin-4-yl)-imidazo[1,2-a]pyridine With sodium t-butanolate In 1,2-dimethoxyethane at 20℃; Stage #2: 2-aminocyclohexanol In 1,2-dimethoxyethane at 100℃; for 2h; Microwave radiation; | 2.8 6-Chloro-3-(2-methoxy-pyridin-4-yl)-imidazo[1,2-a]pyridine (Intermediate G) (1 eq, 200 mg, 0.769 mmol), sodium tert-butoxide (2.4 eq, 1.8 mmol, 177 mg), palladium acetate (17 mg, 0.1 eq), (R)-1-[(lS)-2-(diphenylphosphinojferrocenyljethyldicyclohexylphosphine (43 mg, 0.1 eq) are stirred at RT under an inert atmosphere of argon in DME (3 ml) and degassed thoroughly before adding 2-aminocyclohexanol (2eq, 1.53 mmol, 176 mg) The reaction is heated using microwave radiation at 100 °C for 2 hours. The majority of the solvent is removed in vacuo and the resulting residue is loaded onto a SCX-2 cartridge (resin loading 0.67 mmol/g) eluting with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions are concentrated in vacuo and further purified by flash chromatography (10%MeOH/EtOAc) to afford the title compound; [M+H]+ = 339 |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 94% | Stage #1: ethyl 4-(2-furyl)thiazol-2-carboxylate With water In methanol at 50℃; for 1h; Stage #2: With hydrogenchloride In methanol; water Stage #3: 2-aminocyclohexanol With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In water; N,N-dimethyl-formamide at 20℃; for 3h; | |
| 94% | Stage #1: ethyl 4-(2-furyl)thiazol-2-carboxylate With sodium hydroxide In methanol at 50℃; for 1h; Stage #2: 2-aminocyclohexanol With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 3h; | 568.1 Step 1: Ethyl 4-(2-furyl)thiazol-2-carboxylate (335 mg, 1.50 mmol) obtained in Reference Example 567 was dissolvedin methanol. To the solution was added 4 mol/L of sodium hydroxide aqueous solution (2.5 mL), and the mixturewas stirred at 50°C for 1 hour. After neutralization with hydrochloric acid, the solvent was evaporated under reducedpressure. The resulting residue was dissolved in DMF (5 mL), and 2-aminocyclohexanol (518 mg, 4.50 mmol), EDChydrochloride (864 mg, 4.50 mmol), and 1-hydroxybenzotriazole monohydrate (689 mg, 4.50 mmol) were addedthereto, then the mixture was stirred at room temperature for 3 hours. Water and ethyl acetate were added to thereaction mixture, and the mixture was extracted. The organic layer was washed with brine and dried over anhydrousmagnesium sulfate. The solvent was then evaporated under reduced pressure. The resulting residue was purifiedby silica gel column chromatography (hexane:ethyl acetate = 1:1) to give 4-(2-furyl)-N-(2-hydroxycyclohexyl)thiazole-2-carboxamide (413 mg, 94 %). 1H NMR (CDCl3, δ ppm): 1.26-1.49 (m, 4H), 1.74-1.81 (m, 2H), 2.04-2.16 (m, 2H),3.48-3.55 (m, 1H), 3.78-4.00 (m, 1H), 6.51 (dd, J = 1.8, 3.3 Hz, 1H), 6.81 (dd, J = 0.7, 3.3 Hz, 1H), 7.48 (dd, J =0.7, 1.8 Hz, 1H), 7.61 (s, 1H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 50% | Stage #1: 4,6-dimethyl-1H-indole-2-carboxylic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: 2-aminocyclohexanol In N,N-dimethyl-formamide at 20℃; for 16h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: 2-aminocyclohexanol In ethanol for 1h; Stage #2: With ammonia; hydrogen In ethanol at 160℃; for 16h; Overall yield = 98 %; | 1 Example 1 in a 200 ml reaction kettle, 1 g of the reaction substrate, 2-aminocyclohexanol, was added to 99 g of an ethanol solvent,The concentration of 2-aminocyclohexanol was 1 wt%, and 0.5 g of a supported catalyst Rh / SiO2 (Rh content2% by weight) and stirred for about 1 hour. The atmosphere in the reaction kettle was then replaced with hydrogen, under constant stirringAmmonia gas of 0.4 MPa was charged and dissolved for 1 hour while stirring. Then, 1.5 MPa of hydrogen was charged and reacted at 160 ° C for 15 hours.After completion of the reaction, the resulting product was isolated by distillation to obtain pure, confirmed by gas chromatographyPurity greater than 99%,70% of the trans-isomer was obtained, and the yield was 98%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / -30 - 20 °C 2: pyridinium chlorochromate / dichloromethane / 20 °C 3: diethylamino-sulfur trifluoride / dichloromethane / 24 h / -70 - 20 °C / Inert atmosphere 4: hydrogenchloride / water; methanol / 35 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1.1: n-heptane / 4 h / Reflux 2.1: 15-crown-5; sodium hydroxide / tetrahydrofuran / 9 h / -5 - 20 °C 3.1: hydrogenchloride / toluene / 12 h / -10 - 0 °C 3.2: 12 h / -5 - 0 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80% | With triethylamine In dichloromethane at 20℃; for 16h; | 10 N-(cyclopropylmethyl)-N'-(2-hydroxycyclohexyl)oxamide Preparation 10 N-(cyclopropylmethyl)-N'-(2-hydroxycyclohexyl)oxamide Scheme 2, step B: Add TEA (115 mL, 0.8 mol) to a solution of ethyl 2-(cyclopropylmethylamino)-2-oxo-acetate (128.5 g, 0.75 mol) in DCM (1.6 L) at ambient temperature. Add 2-aminocyclohexanol (91 g, 0.8 mol) to the mixture and stir for 16 hr at ambient temperature. Filter the resulting precipitate and air dry to give the title compound (147 g, 80%) as a white solid mixture of cis and trans isomers. LC-ES/MS (m/z) 241.1 (M+H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 19% | With triethylamine In ethyl acetate at 20 - 80℃; for 4h; | 1 N-allyl-N'-(2-hydroxycyclohexyl)oxamide Preparation 1 N-allyl-N'-(2-hydroxycyclohexyl)oxamide Scheme 1, step A: Combine 2-aminocyclohexanol (7.7 g, 66.8 mmol), ethyl-2-(allylamino)-2-oxo-acetate (10.0 g, 63.6 mmol) and triethylamine (9.8 mL, 70.0 mmol) in EtOAc (127.3 mL) and heat the mixture at 80° C. for 4 hr. Cool the mixture to ambient temperature and stir overnight. Isolate the resulting precipitate by vacuum filtration, wash the filter cake with EtOAc, and dry for 4 hr to give the title compound (7.2 g, 50%) as a white, crystalline solid. Concentrate the filtrate under reduced pressure and sonicate the resulting solid in Et2O. Isolate the solid by vacuum filtration, wash the filter cake with Et2O, and dry for 1.5 hr to give an additional lot of the title compound (2.8 g, 19%) as a white, crystalline solid. The product is a mixture of cis and trans isomers. LC-ES/MS (m/z): 227.0 (M+H). |
| 10 g | With triethylamine In ethanol at 80℃; for 4h; | 1.A Scheme 1, step A Combine 2-aminocyclohexanol (7.7 g, 66.8 mmol), ethyl-2-(allylamino)-2-oxo-acetate (10.0 g, 63.6 mmol, Matrix Scientific, CAS 52781-10-9) andTEA (9.8 mL, 70.0 mmol) in EtOH (127.3 mL) and heat the mixture at 80 °C for 4 hr. Cool the mixture to ambient temperature and stir overnight. Isolate the resulting precipitate by vacuum filtration, wash the filter cake with EtOAc, and dry for 4 hr to obtain the title compound (7.2 g, 50% yield) as a white, crystalline solid. Evaporate thefiltrate under reduced pressure and sonicate the resulting solid in Et20. Collect the solid by vacuum filtration, wash the filter cake with Et20, and dry for 1.5 hr to give an additional lot of the title compound (2.8 g, 19% additional yield) as a white, crystalline solid. The product is a mixture of cis and trans isomers. ES/MS (m/z): 227.0 (M+H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 56% | With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 4h; Inert atmosphere; | 39.4 Step-4: To a solution of 4-[4-(2-chloropyridin-4-yl)-benzyl]-pyrrolo[l,2-h]pyridazine-2- carboxylic acid(4l.O mg, 0.11 mmol) in DCM (5.0 mL) at 0 to 5 °C under N2, DIPEA (0.04 mL, 0.23mmol),TBTU (40.0 mg, O.l2mmol) and l-amino-2-hydroxy-cyclohexane( 13.0 mg, O. l lmmol) were added sequentially. The reaction mass was gradually warmed to r.t, and was stirred for 4 h. The reaction mixture was quenched with ice water (5.0 mL) and was extracted with DCM (10 mL x 2). Organic layer was washed with brine solution (50 mL), dried over anhydrous Na2S04 and the solvent was evaporated under reduced pressure to obtain the crude compound which was purified by flash chromatography using to afford the title compoundN- [( 1 S ,2S )-2-Hydroxycyclohexyl] -4- [4-(2-chloropyridin-4-yl)-benzyl] -pyrrolo [ 1 ,2b]pyridazine- 2- carboxamide(29.0 mg) in 56% yield.1H - NMR (400 MHz, CDCl3): 58.43 (d, J = 5.2 Hz, 1H), 7.75 (s, 1H), 7.56 (d, J =7.9 Hz, 2H), 7.51 (s, 1H), 7.40 (d, J =7.9 Hz, 2H), 7.40 (d, J = 5.2 Hz, 1H), 7.19 (s, 1H), 6.95 (dd, J = 1.9, 4.0 Hz, 1H), 6.60 (d, J = 4.0 Hz, 1H), 4.22 (s, (0279) 2H), 3.88-3.78 (m, 1H), 3.55-3.46 (m, 1H), 3.02 (d, J = 4.4 Hz, 1H), 2.18-2.07 (m, 2H), 1.85-1.75 (m, 2H), 1.45-1.25 (m, 4H); Mass (m/z); 461.1 (M+H)+. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 48.08% | 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 dichloromethane at 4℃; for 4h; | 1.61 Into a 100-mL round-bottom flask, was placed N-(2-(4-methoxypyridin-2-yl)- 6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-N-methylglycine (150.00 mg, 0.477 mmol, 1.00 equiv), 2-aminocyclohexan-1-ol (82.44 mg, 0.716 mmol, 1.50 equiv), HATU (272.16 mg, 0.716 mmol, 1.5 equiv), DIEA (185.02 mg, 1.432 mmol, 3 equiv), and DCM (20.00 mL). The resulting solution was stirred for 4 hr at 4°C. The resulting solution was extracted with 3x20 mL of dichloromethane and the organic layers were combined, dried in an oven under reduced pressure, and concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions (2SHIMADZU (HPLC-01)): Column, Atlantis HILIC OBD Column, 19*150mm*5um; mobile phase, Water (0.05%NH3H2O) and ACN (5% PhaseB up to 18% in 8 min). This resulted in 95.2 mg (48.48%) of N-((1R,2R)-2-hydroxycyclohexyl)-2-((2-(4-methoxypyridin-2-yl)-6,7- dihydro-5H-cyclopenta[d]pyrimidin-4-yl)(methyl)amino)acetamide as a white solid.1H NMR (300 MHz, DMSO-d6) δ 8.48 (d, J = 5.6 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.82 (d, J = 2.6 Hz, 1H), 7.04 (dd, J = 5.7, 2.6 Hz, 1H), 4.54 (d, J = 4.8 Hz, 1H), 4.25 (d, J = 16.4 Hz, 1H), 4.15 (d, J = 16.3 Hz, 1H)3.89 (s, 3H), 3.48-3.36 (m, 1H), 3.31-3.22 (m, 4H), 3.14 (t, J = 4.7 Hz, 2H), 2.82 (t, J = 7.9 Hz, 2H), 2.03-1.93 (m, 2H), 1.86-1.49 (m, 4H), 1.32-1.05 (m, 4H). LCMS (ES) [M+1] + m/z: 412.3. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 44.7 % | In ethanol at 100℃; | 10.1 Step 1: Synthesis of 2-((4-bromophthalazin-1-yl)amino)cyclohexanol A solution of 1,4-dibromophthalazine (100 mg, 347 mmol) and 2-aminocyclohexanol (40.0 mg, 347 mmol) in EtOH (3.00 mL) was stirred at 100°C for 24 hours.The reaction solution is cooled to room temperature, solid precipitates, filter, and the filter cake is dried under reduced pressure.The target compound (50.0 mg, yield 44.7%, white solid) was obtained and used directly in the next step. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 55 % | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In tetrahydrofuran at 20℃; | 4.11.13. 2-(4-Ethoxyphenyl)-N-(7-((2-hydroxycyclohexyl)amino)-7-oxoheptyl)-9-(2-methoxyphenyl)-8-oxo-8,9-dihydro-7H-purine-6-carboxamide (11) The coupling reaction of acid 3 (107 mg, 0.2 mmol) with 2-aminocyclohexanol(as a mixture of cis and trans isomers, 23 mg, 0.2 mmol) wasperformed in THF (2 mL) in the presence of HOBt hydrate (46 mg, 0.3mmol), EDCI hydrochloride (58 mg, 0.3 mmol) and Et3N (0.11 mL, 0.8mmol) at room temperature for 12 h to give compound 11 as solids (70mg, 55% yield). The purity of compound 11 was 95.3%, as shown byHPLC on an HC-C18 column (Merck, 4.6 × 100 mm, 2 μm particle size),tR = 8.0 min [MeOH/(0.1% TFA aqueous solution) = 6.5:3.5] at a flowrate of 1.0 mL/min. C34H42N6O6; white solid; mp = 199-200 C; TLC(CH2Cl2/MeOH = 98:2) Rf = 0.15; IR νmax (KBr) 3290, 2932, 2862,1735, 1654, 1598, 1509, 1474, 1400, 1248, 1164, 1052 cm 1; 1H NMR(400 MHz, CDCl3) δ 9.90 (1 H, s), 8.19 (2 H, d, J = 8.9 Hz), 8.04 (1 H, t, J= 6.2 Hz), 7.47 (1 H, td, J = 8.4, 1.6 Hz), 7.40 (1 H, d, J = 7.5 Hz),7.12-7.08 (2 H, m), 6.96 (2 H, d, J = 8.9 Hz), 5.93 (1 H, d, J = 7.1 Hz),4.04 (2 H, q, J = 7.0 Hz), 3.76 (3 H, s), 3.65-3.50 (3 H, m), 3.34-3.27 (1H, m), 2.21-2.16 (2 H, m), 2.06-1.90 (3 H, m), 1.70-1.63 (6 H, m),1.41-1.07 (11 H, m); 13C NMR (100 MHz, CDCl3) δ 174.9, 164.3, 160.9,156.7, 155.5, 153.6, 152.9, 132.5, 130.8, 129.8, 129.6, 129.3 (2×),120.9, 120.5, 119.1, 114.2 (2×), 112.5, 75.1, 63.5, 55.9, 55.7, 38.9,36.4, 34.5, 31.5, 29.4, 28.3, 26.1, 25.4, 24.6, 24.1, 14.7; ESI-HRMS calculated for C34H43N6O6: 631.3239 found: m/z 631.3237 [M + H]+. |
| 55 % | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In tetrahydrofuran at 20℃; | 4.11.13. 2-(4-Ethoxyphenyl)-N-(7-((2-hydroxycyclohexyl)amino)-7-oxoheptyl)-9-(2-methoxyphenyl)-8-oxo-8,9-dihydro-7H-purine-6-carboxamide (11) The coupling reaction of acid 3 (107 mg, 0.2 mmol) with 2-aminocyclohexanol(as a mixture of cis and trans isomers, 23 mg, 0.2 mmol) wasperformed in THF (2 mL) in the presence of HOBt hydrate (46 mg, 0.3mmol), EDCI hydrochloride (58 mg, 0.3 mmol) and Et3N (0.11 mL, 0.8mmol) at room temperature for 12 h to give compound 11 as solids (70mg, 55% yield). The purity of compound 11 was 95.3%, as shown byHPLC on an HC-C18 column (Merck, 4.6 × 100 mm, 2 μm particle size),tR = 8.0 min [MeOH/(0.1% TFA aqueous solution) = 6.5:3.5] at a flowrate of 1.0 mL/min. C34H42N6O6; white solid; mp = 199-200 C; TLC(CH2Cl2/MeOH = 98:2) Rf = 0.15; IR νmax (KBr) 3290, 2932, 2862,1735, 1654, 1598, 1509, 1474, 1400, 1248, 1164, 1052 cm 1; 1H NMR(400 MHz, CDCl3) δ 9.90 (1 H, s), 8.19 (2 H, d, J = 8.9 Hz), 8.04 (1 H, t, J= 6.2 Hz), 7.47 (1 H, td, J = 8.4, 1.6 Hz), 7.40 (1 H, d, J = 7.5 Hz),7.12-7.08 (2 H, m), 6.96 (2 H, d, J = 8.9 Hz), 5.93 (1 H, d, J = 7.1 Hz),4.04 (2 H, q, J = 7.0 Hz), 3.76 (3 H, s), 3.65-3.50 (3 H, m), 3.34-3.27 (1H, m), 2.21-2.16 (2 H, m), 2.06-1.90 (3 H, m), 1.70-1.63 (6 H, m),1.41-1.07 (11 H, m); 13C NMR (100 MHz, CDCl3) δ 174.9, 164.3, 160.9,156.7, 155.5, 153.6, 152.9, 132.5, 130.8, 129.8, 129.6, 129.3 (2×),120.9, 120.5, 119.1, 114.2 (2×), 112.5, 75.1, 63.5, 55.9, 55.7, 38.9,36.4, 34.5, 31.5, 29.4, 28.3, 26.1, 25.4, 24.6, 24.1, 14.7; ESI-HRMS calculated for C34H43N6O6: 631.3239 found: m/z 631.3237 [M + H]+. |

A229214 [6936-47-6]
cis-2-Aminocyclohexanol hydrochloride
Similarity: 0.96

A261554 [190792-72-4]
(1R,2S)-2-Aminocyclohexanol hydrochloride
Similarity: 0.96

A314196 [200352-28-9]
(1S,2R)-2-Aminocyclohexanol hydrochloride
Similarity: 0.96

A229214 [6936-47-6]
cis-2-Aminocyclohexanol hydrochloride
Similarity: 0.96

A261554 [190792-72-4]
(1R,2S)-2-Aminocyclohexanol hydrochloride
Similarity: 0.96

A314196 [200352-28-9]
(1S,2R)-2-Aminocyclohexanol hydrochloride
Similarity: 0.96

A229214 [6936-47-6]
cis-2-Aminocyclohexanol hydrochloride
Similarity: 0.96

A261554 [190792-72-4]
(1R,2S)-2-Aminocyclohexanol hydrochloride
Similarity: 0.96

A314196 [200352-28-9]
(1S,2R)-2-Aminocyclohexanol hydrochloride
Similarity: 0.96