Structure of 1228014-10-5
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CAS No. : | 1228014-10-5 |
Formula : | C17H30BNO3Si |
M.W : | 335.32 |
SMILES Code : | CC(C1=NC=C(B2OC(C)(C)C(C)(C)O2)C=C1)(O[Si](C)(C)C)C |
MDL No. : | MFCD12198135 |
InChI Key : | GQSLZAFZAPLKEY-UHFFFAOYSA-N |
Pubchem ID : | 53398358 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 23 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.71 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 98.55 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.58 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 |
3.54 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.36 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.3 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.44 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.93 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.08 |
Solubility | 0.028 mg/ml ; 0.0000835 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.08 |
Solubility | 0.0281 mg/ml ; 0.0000838 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.42 |
Solubility | 0.00127 mg/ml ; 0.00000378 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
Yes |
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) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.83 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 |
0.0 |
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 |
1.0 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) |
3.84 |
* 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 |
---|---|---|
93% | With sodium carbonate;PdCl2(AmPhos)3; In N,N-dimethyl-formamide; at 70℃; for 1.5h; | Ethyl 2-(3,5-dibromopyrazin-2-ylamino)acetate (1 equiv) and trans-4- methoxycyclohexanamine.hydrochloride (1.5 equiv), NMP and DIEA were combined and heated to 127 0C and maintained at that temperature for 18 h. Upon reaction completion, the mixture was cooled to 35 0C over 4 h. The batch was transferred to a mixture of ethyl acetate and 5 % brine. The aqueous layer was removed and the organic layer containing the batch was washed successively with 5 % brine and water. The organic layer containing the batch was concentrated by vacuum distillation to a low volume, cooled to ambient temperature and the solids were collected by vacuum filtration. The filter cake was washed with MTBE and the product was dried in a vacuum to give 41% yield of ethyl 2-(5-bromo- 3-(trans-4-methoxycyclohexylamino)pyrazin-2-ylamino) acetate. A mixture of ethyl 2-(5- bromo-3-(trans-4-methoxycyclohexylamino)pyrazin-2-ylamino) acetate (1 equiv), water and 85 % phosphoric acid (3:1) was heated to 80 0C over 1 h. Heating was maintained for 18 h to effect reaction completion. Upon reaction completion, the mixture was cooled to 25 0C and filtered to give a crude product as tan solid. The resulting solids were washed with water, slurried in water and filtered. The filter cake was washed with water until the pH of the filtrate was between 4 and 8. The resulting material was dried under vacuum to give 89 % yield of 7-bromo-l-(trans-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin- 2(lH)-one. 7-Bromo-l-(trans-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin- 2(lH)-one (1 equiv), 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-2-(2- (trimethylsilyloxy)propan-2-yl)pyridine (1 equiv), sodium carbonate (3 equiv) and PdCl2(AmPhOs)2 (0.003 equiv) were combined in isopropanol and heated at 70 0C for 1.5 h. Standard work-up and purification afforded the protected compound in 93 % yield. Deprotection using standard conditions for removal of a trimethylsilyl-group and isolation gave the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 7h;Inert atmosphere; | {1-[5-(1-[2-(Difluoromethoxy)phenyl]methyl}-5-fluoro-2-methylbenzimidazol-6-yl)-pyridin-2-yl]-1-methylethoxy}(trimethyl)silane Intermediate 147 (185 mg, 0.55 mmol) and Intermediate 50 (175 mg, 0.45 mmol) were dissolved in anhydrous 1,4-dioxane (8 mL) and 2M aqueous potassium carbonate solution (0.7 mL) was added. The mixture was degassed under nitrogen for 5 minutes. Pd(dppf)Cl2 complex with DCM (20 mg, 0.024 mmol) was added. The mixture was stirred at 100 C. under nitrogen for 7 h. The reaction mixture was allowed to cool, dried over sodium sulfate and concentrated under vacuum to give crude product as a dark oil (318 mg). This material was loaded onto a 10 g HP-silica cartridge and eluted on a Biotage Isolera 4, from a 0-70% ethyl acetate in heptane gradient, to afford the title compound (166 mg, 71%) as a colourless oil. deltaH (500 MHz, CDCl3) 8.61 (s, 1H), 7.85 (d, J 8.0 Hz, 1H), 7.72 (d, J 8.2 Hz, 1H), 7.53 (d, J 10.8 Hz, 1H), 7.37-7.29 (m, 1H), 7.21-7.14 (m, 2H), 7.13-7.06 (m, 1H), 6.80-6.45 (m, 2H), 5.43-5.37 (m, 2H), 2.61 (s, 3H), 1.65 (s, 6H), 0.17 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80 - 100℃; for 2h;Inert atmosphere; Sealed tube; | 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-{2-[(trimethylsilyl)oxy]propan-2-yl}pyridine In a pressure tube, a stirring solution of Intermediate 146 (200 mg, 0.69 mmol) in 1,4-dioxane (8 mL) was treated with bis(pinacolato)diboron (211 mg, 0.83 mmol) and potassium acetate (205 mg, 2.09 mmol). The stirring mixture was degassed with nitrogen for 10 minutes, then Pd(dppf)Cl2 complex with DCM (29 mg, 0.04 mmol) was added. The pressure tube was sealed and the contents were stirred at 80 C. for 1 h, then at 100 C. for 1 h. The reaction mixture was allowed to cool and then filtered through celite, washing with ethyl acetate (30 mL). The filtrate was concentrated under vacuum to give a dark brown oil, which was triturated in 2:1 ether:heptane (10 mL). The suspension was filtered and the filtrate concentrated in vacuo to give a brown oil which was loaded onto a 10 g HP-silica cartridge and eluted on a Biotage Isolera 4, from a 0-100% ethyl acetate in heptanes gradient, to afford the title compound (185 mg, 80%) as a light brown solid. deltaH (500 MHz, CDCl3) 8.85 (s, 1H), 8.03 (d, J 7.8 Hz, 1H), 7.64 (d, J 7.9 Hz, 1H), 1.61 (s, 6H), 1.34 (s, 12H), 0.14 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: Prepared from Intermediate 21 and 5 -(4,4,5,5 -tetramethyl- 1,3 ,2-dioxaborolan-2- yl)-2- {2- [(trimethylsilyl)oxy]propan-2-yl} pyridine by a method analogous to that used to prepare Example 1, followed by treatment with TBAF at room temperature. H (500MHz, DMSO-d6) 8.82 (d,J2.2 Hz, 1H), 8.75 (s, 1H), 8.04 (dd,J8.3, 2.4 Hz, 1H), 7.78(d,J8.2 Hz, 1H), 7.63 (dd,J9.3, 1.7 Hz, 1H), 7.57 (d,J9.3 Hz, 1H), 7.19 (d,J8.3 Hz,1H), 7.06 (td,J8.3, 5.7 Hz, 1H), 7.00 (t,J8.7 Hz, 1H), 5.64 (s, 2H), 5.31 (s, 1H), 4.88 (s,2H), 2.39 (s, 3H), 1.50 (s, 6H). LCMS m/z 447. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example B5.18 2-(5-{5-[(4-Chlorophenyl)sulfanyl]-2-[cis-4-(hydroxymethyl)cyclohexyl]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-olTo a mixture of bromide (43.0 mg, 0.107 mmol), <strong>[1228014-10-5]5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-{2-[(trimethylsilyl)oxy]propan-2-yl}pyridine</strong> (40.5 mg, 0.160 mmol), tetrakis(triphenylphosphine)palladium(0) (12.3 mg, 10.7 mumol) in toluene (2000 mul) was added K2CO3 (267 mul, 0.534 mmol) and heated in oil bath at 120 C. for 12 h. The reaction was diluted with CH2Cl2, dried over Na2SO4, filtered and conc. The residue was dissolved in THF (1 mL) and treated with TBAF (107 mul, 0.107 mmol) for 1 h. The solvent was removed and the residue was purified by reverse-phase HPLC (C-18, 20-80% MeCN in H2O, with 0.05% TFA) to provide product as a white solid. 1H NMR (CDCl3, 400 MHz) delta 9.37 (s, 1H), 8.86-8.82 (m, 1H), 7.72 (d, J=8.8 Hz, 1H), 7.31-7.27 (m, 2H), 7.22-7.19 (m, 2H), 4.24 (d, 6.0 Hz, 1H), 3.54 (d, J=6.0 Hz, 1H), 2.87-2.78 (m, 1H), 2.27-2.20 (m, 2H), 2.00-1.96 (m, 2H), 1.71 (s, 6H), 1.70-1.43 (m, 3H), 1.26-1.09 (m, 2H). FIRMS (ES) [M+1]+ calcd for C24H28ClN2O3S: 459.1504. Found: 459.1498. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example B5.12-(5-{5-[(4-Chlorophenyl)sulfanyl]-2-(tetrahydro-2H-pyran-4-yl)-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-olTo a mixture of B5 (540 mg, 1.44 mmol), tetrakis(triphenylphosphine)palladium(0) (83.0 mg, 0.0720 mmol), and <strong>[1228014-10-5]5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-{2-[(trimethylsilyl)oxy]propan-2-yl}pyridine</strong> (438 mg, 1.73 mmol) in toluene (11.5 mL) was added 2.0 M aqueous solution of K2CO3 (2.2 mL). The resulting mixture was heated at 160 C. in a microwave for 1 h. The process was repeated three more times until the starting material consumed. The reaction mixture was diluted with dichloromethane, dried over Na2SO4 and filtered. The filtrate was concentrated and dissolved in THF (10.7 mL) and treated with TBAF (1.1 mL, 1M in THF) at room temperature for 1 h. The solvent was removed and the residue was purified by silica gel flash chromatography (5-70% EtOAc in hexanes), followed by reverse-phase HPLC (C-18, 20-90% MeCN in H2O, with 0.05% TFA) and a final purification by silica gel flash chromatography (10-70% EtOAc in hexanes) to provide the title compound as a clear oil. The product turned into a white solid after converting to the HCl salt foam. 1H NMR (CDCl3, 400 MHz) delta 9.18 (dd, J=1.2, 2.0, Hz, 1H), 8.33 (dd, J=2.0, 8.4 Hz, 1H), 7.42 (dd, J=1.2, 8.4 Hz, 1H), 7.29-7.238 (m, 2H), 7.16-7.13 (m, 2H), 4.85 (s, 1H), 4.06 (td, J=3.6, 8.4 Hz, 2H), 3.55 (dt, J=3.2, 10.8 Hz, 2H), 3.12 (m, 1H), 2.07-1.94 (m, 4H), 1.56 (s, 6H). HRMS (ES) [M+1]+ calcd for C22H24ClN2O3S: 431.1191. Found: 431.1198. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine tetrafluoroborate; In 1,4-dioxane; water; at 20 - 105℃; for 1h; | A degassed mixture of Example 10 (299 mg, 0.56 mmol), 6-(2-(trimethylsilyloxy)propan- 2-yl)pyridine-3-boronic acid pinacol ester (295 mg, 0.84 mmol),tris(dibenzylideneacetone)dipalladium(0) (26.0 mg, 0.03 mmo 1), potassium phosphate tribasic (296 mg, 1.40 mmol), and tricyclohexylphosphonium tetrafluoroborate (26.0 mg, 0.07 mmol) in 1,4-dioxane (4.5 mL) and water (0.5 mL) was heated to 105 C overnight. The reaction mixture was cooled to r.t, diluted with EtOAc (50 mL) and washed with water (2 x 50 mL). The organic layer was dried (Na2SO4), filtered and concentrated invacuo. The residues were dissolved in DCM (4 mL) and 4M HC1 solution (1.5 mL) was added. The solution was stirred at r.t for 1 hour. Saturated aqueous sodium carbonate solution (50 mL) was added, and the aqueous layer separated. The organic layer was washed with brine (50 mL), dried (Na2504), filtered and concentrated in vacuo to give a crude oil. The crude material was purified by column chromatography, eluting with 0-100% EtOAc in DCM, followed by 0-10% MeOH in EtOAc to give the title compound as an off-white powder (105 mg, 38% yield).1H NMR (400 MHz, DMSO) oe 9.15 (d, 1 H, J = 6.8 Hz), 8.61 (s, 1 H), 8.26-8.21 (m, 1 H), 7.90 (dt, 1 H, J = 1.9, 8.2 Hz), 7.77 (d, 1 H, J= 8.2 Hz), 7.61 (t, 1 H, J = 75 Hz), 7.61 (d, 1 H, J 11.5 Hz), 7.52-7.50 (m, 3 H), 6.34 (d, 1 H, J 7.1 Hz), 5.27 (s, 1 H), 4.91 (t,1 H, J = 6.8 Hz), 3.52-3.45 (m, 1 H), 2.75 (d, 1 H, J = 13.4 Hz), 1.49 (s, 6 H). LCMS Method 3 ESI MH+ 495.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine tetrafluoroborate; In 1,4-dioxane; water; at 105℃;Inert atmosphere; | Example 11 (750 mg, 2.00 mmol), 6-(2-(trimethylsilyloxy)propan-2-yl)pyridine-3- boronic acid pinacol ester (1.41 g, 4.00 mmol), tris(dibenzylideneacetone)dipalladium(0) (94 mg, 0.1 mmol) and tricyclohexylphosphonium tetrafluoroborate (91 mg, 0.24 mmol,97 mass%) were added to a round bottom flask, evacuated & refilled with nitrogen and1 ,4-dioxane (10 mL) added followed by potassium phosphate (1.27 g, 6.00 mmol) in water (1 mL). The mixture was degassed, placed under nitrogen and heated to 105C overnight. The mixture was partitioned between EtOAc and water, the organic layer dried over sodium sulphate, filtered and concentrated in vacuo. The crude material was purifiedby chromatography, (EtOAc to 15% MeOH gradient). The product fractions were concentrated in vacuo to give the title compound as an off-white solid, (1.05 g, 96% yield). LC/MS Method 3: RT 1.61 minutes, mlz 549. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine tetrafluoroborate; In 1,4-dioxane; water; at 105℃; for 18h;Microwave irradiation; | Example 11 (140 mg, 0.373 mmol) and 6-(2-(trimethylsilyloxy)propan-2-yl)pyridine-3- boronic acid pinacol ester (171 mg, 0.484 mmol) were added to a small microwave tube and tris(dibenzylideneacetone)dipalladium(0) (17.6 mg, 0.0 186 mmol) and tricyclohexylphosphonium tetrafluoroborate (17.0 mg, 0.0447 mmol) were added withdioxane (2 mL), followed by K3P04 (158 mg, 0.745 mmol) in water (1 mL). The mixture was degassed and heated to 105C for 18 hours. The mixture was diluted with EtOAc (30 mL) and washed with water (10 mL). The organic was concentrated in vacuo, redissolved in DCM (10 mL) and 4.OM HC1 in dioxane (5 mL) added and the mixture was stirred at r.t for 1 hour. The mixture was partitioned between DCM and sodium carbonate(20 mL). The organic phase was dried (Na2SO4), filtered and concentrated in vacuo.Purification by preparative HPLC gave the title compound (35 mg, 20%) as a white solid.1HNMR: (d6-DMSO 300 MHz) oe:1.48 (s, 6 H), 2.74 (d, 1H, J=13.3 Hz), 3.49 (m, 1H),4.88 (t, 1H, J=6.7 Hz), 5.24 (s, 1H), 6.35 (d, 1H, J7.0 Hz), 7.49-7.53 (m, 3H), 7.69-7.72(m, 3H), 7.66 (t, 1H, JHF73.2Hz), 7.97 (dd, 1H, J = 5.6, 8.2 Hz), 8.21-8.24 (m, 1H),8.73 (d, 1H, J 1.8 Hz), 9.13 (d, 1H, 6.8 Hz). LC/MS Method 3: RT 1.76 mins (pH 10),mlz 477. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; chloro(2-dicyclohexylphosphino-2?,6?-diisopropoxy-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II) 2nd generation; In tetrahydrofuran; at 50℃; for 2h;Inert atmosphere; | To a solution of 7-chloro- 1 -isopropyl-N- [(6-methyl-2-oxo-4-propyl- 1 ,2-dihydropyridin-3- yl)methyl]imidazo[1,5-a]pyridine-5-carboxamide (intermediate 202A) (250 mg, 0.62 mmol) and 5-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)-2- { 2- [(trimethylsilyl)oxy]propan-2-yl }pyridine (241 mg, 0.75 mmol) in tetrahydrofuran (10 ml) under an atmosphere of nitrogen was added potassium phosphate (0.5 M, 4.2 ml), followed by a solution of (2?-aminobiphenyl-2- yl)(chloro)dicyclohexyl(2?,6?-diisopropoxybiphenyl-2-yl)palladium (2? generation Ruphos precatalyst) (98 mg, 125 mmol) in tetrahydrofuran (0.5 ml), and the reaction was stirred at 50 Cfor 2 h. Water was added, the phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was taken to the next step without purification.LCMS (conditions 2.4): Rt 1.40 mm; MS (ESI): [M + H] = 574.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; water; sodium carbonate; In 1,4-dioxane; at 85℃; for 16h;Inert atmosphere; | [0570] A mixture of crude Example 122c (150 mg, 0.3 mmol), Example d (100 mg, 0.3 mmol), Pd(dppf)Cl2 (23 mg, 0.03 mmol) and Na2C03 (100 mg, 0.9 mmol) in Dioxane/H20(3 mL/1 mL) was exchange N2 for 3 times. After stirred at 85C for 16 h at N2, the mixture was concentrated under reduced pressure, which was purified by Pre-TLC (Petroleum DCM/MeOH = 10/1) to give Example 126 38 mg, yield 25%) as a yellow solid. LCMS [M+l] + = 500. [0571] 1H NMR (400 MHz, DMSO-d 6) delta 12.59 (s, 1H), 8.88 (s, 1H), 8.60 (d, J= 2.4 Hz, 1H), 8.48 (s, 1H), 8.36 (d, J= 8.3 Hz, 1H), 8.01 (t, J= 8.0 Hz, 1H), 7.90 (dd, J= 8.2, 2.4 Hz, 1H), 7.81 (d, J= 7.5 Hz, 1H), 7.74 (d, J= 8.2 Hz, 1H), 5.35-5.28(m,lH), 5.27 (s, 1H), 4.26 (t,J= 7.4 Hz, 2H), 3.34 (d, J= 2.7 Hz, 2H), 2.29 - 2.03 (m, 2H), 1.52 (d, J= 6.7 Hz, 6H), 1.46 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34.26 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 80℃;Inert atmosphere; | [0435] A mixture of Example 66a (50 mg, 0.11 mmol), Example 66b (43.1 mg, 0.13 mmol) in Dioxane/H20 (2mL, 10: 1) was added Pd(dppf)Cl2 (5 mg, 0.0068 mmol) and Na2C03(34.26 mg, 0.33 mmol). Then the mixture was degassed by bubbling N2 through the solution for 2 min using a syringe needle. After that, the mixture was heated at 80Covernight. LCMS [M+l]+ = 546.1 |