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CAS No. : | 4426-47-5 | MDL No. : | MFCD00002106 |
Formula : | C4H11BO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | QPKFVRWIISEVCW-UHFFFAOYSA-N |
M.W : | 101.94 | Pubchem ID : | 20479 |
Synonyms : |
|
Num. heavy atoms : | 7 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 1.0 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 30.48 |
TPSA : | 40.46 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.24 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 0.96 |
Log Po/w (WLOGP) : | 0.26 |
Log Po/w (MLOGP) : | -0.18 |
Log Po/w (SILICOS-IT) : | -1.36 |
Consensus Log Po/w : | -0.06 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.88 |
Solubility : | 13.5 mg/ml ; 0.132 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.4 |
Solubility : | 4.09 mg/ml ; 0.0401 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -0.3 |
Solubility : | 51.4 mg/ml ; 0.505 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.44 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313 | UN#: | N/A |
Hazard Statements: | H315-H319 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene;Heating / reflux; | To a solution of (S)-CBS ligand (11.53 g, 45.5 mmol) in toluene (110 mL) was added butylboronic acid (5.1 g, 47.8 mmol) and the mixture was heated to reflux over night with a Dean stark. This final solution was 0.48 M and was used directly. | |
In toluene;Heating / reflux; | A. Synthesis of butyl-(S)-CBS in toluene: To a solution of (S)-CBS ligand (11.53 g, 45.5 mmol) in toluene (110 mL) was added butylboronic acid (5.1 g, 47.8 mmol) and the mixture was heated to reflux over night with a Dean stark. This final solution was 0.48 M and was used directly. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With dichloro bis(acetonitrile) palladium(II); triphenyl-arsane; silver(l) oxide In tetrahydrofuran for 18h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With potassium carbonate In xylene at 130℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23% | With sodium hydroxide;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; for 21h;Heating / reflux; | To a stirring solution of n-butane boronic acid (0.133 g, 1.3 mmol, 1.4 equ) and dichloropalladium (dppf) (0.050 g, 0.06 mmol, 0.07 eq) in tetrahydrofuran (7 ml) and 3M NaOH solution (1.1 ml) was added 34 (0.500 g, 0.9 mmol) added and the reaction heated to reflux for 21 hours. The reaction was then quenched with water and diethyl ether. The organic layer was collected and the aqueous layer extracted with diethyl ether (2x). The combined organic layers were washed with 1M HC1 and brine then dried [(MGS04)] and concentrated in vacuo to give a yellow oil. A silica plug (dichloromethane) yielded 39d (0.099 g, [23 %)] as an orange oil. EI+ 474.2 [(15T,] [M+)] [C29H3006] Calc. 474. 2042 Found 474.2041. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With sodium hydroxide;triisopropyl phosphite; palladium diacetate; In tetrahydrofuran; water; isopropyl alcohol; at 105℃;Product distribution / selectivity; | Example 14:Suzuki coupling of 4-bromobenzotrifluoride with butaneboronic acid with catalysis by triisopropyl phosphite-palladium complexWith exclusion of air, 0.225 g of 4-bromobenzotrifluoride (1.0 mmol), 0.122 g of butaneboronic acid (1.2 mmol), 21 mg of triisopropyl phosphite (0.1 mmol, 10 mol %), 11 mg of palladium(II) acetate (0.05 mmol, 5 mol %) and 1 ml of 3N sodium hydroxide solution (3 mmol) in 5 ml of a 19:1:20 tetrahydrofuran/water/isopropanol mixture were heated to 105 C. with stirring until the conversion (according to GC) was complete. The mixture was allowed to cool, the reaction mixture was extracted with 4 ml of 2N NaOH and the organic phase was removed. Filtration through silica gel (eluent: ethyl acetate) afforded 0.186 g (0.92 mmol, 92%) of 4-butyltrifluoromethylbenzene. |
92% | With potassium phosphate;triisopropyl phosphite; palladium diacetate; In 1,4-dioxane; at 105℃;Product distribution / selectivity; | Example 15: as Example 14, except that the base used was 637 mg (3 mmol) of anhydrous potassium phosphate in place of sodium hydroxide solution and the solvent used was dioxane. The yield was 92%. |
86% | With potassium phosphate;triisopropyl phosphite; nickel dichloride; In 1,4-dioxane; at 105℃;Product distribution / selectivity; | Example 16: as Example 15, except that 6.5 mg (0.05 mmol) of anhydrous nickel(II) chloride were used instead of palladium acetate. 86% product was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; tricyclohexylphosphine;palladium diacetate; In toluene; at 100℃; for 5h; | To the product from Example 3A, Step 2 (55 mg, 0.1 mmol) in toluene (2 ml) and water (0.1 ml) were added <strong>[4426-47-5]butylboronic acid</strong> (15 mg, 0. 134 mmol), potassium phosphate (75 mg, 0.35 MMOL), TRICYCLOHEXYLPHOSPHINE (3 mg, 0.01 mmol) and palladium acetate (3 mg, 0.01 mmol). The mixture was degassed, placed under nitrogen and heated at 100C for 5H. After cooling the reaction was diluted with EtOAc (50 ml), passed through Celite and the filtrate washed with water (20 ml), brine (20 ml), dried (MGS04), filtered and evaporated. The crude product was purified by flash chromatography eluting with'hexane to 20: 1 IHEXANE/ETHER to give a colourless oil (25 mg) as a mix of diastereoisomers. To this ester (25 mg, 0.045 mmol) in THF (5 ml) under nitrogen was added a solution of lithium hydroxide (7 mg, 0. 32 mmol) in water (1 ml). The reaction was stirred for 18 H and then diluted with water (30 ml), made acidic with hydrochloric acid (aqueous, 2 M) and extracted with EtOAc (3 x 20 ml). The organic extracts were washed with brine, dried (MGS04), filtered and evaporated. The crude product was purified by flash chromatography eluting with 4: 1 IHEXANE/ETHYL acetate to 1: 1HEXANE/ETHYL acetate to give (6-Butyl-9- {l- [4- (trifluoromethyl) phenyl] PROPYL}-2, 3,4, 9-TETRAHYDRO-1 H-CARBAZOL-1-YL) acetic acid as a white solid (18 mg) as a 1 : 1 mix OF DIASTEREOISOMERS. 1H NMR (CDC13) 7.54 (1H, J = 7.8 Hz), 7. 48 (1H, J = 7.9 Hz), 7.24 (4H, M), 6.79 (1H, M), 5.41 (1H, t, J = 8.1 Hz), 3.50 (0.5 H, M, diastereomer A), 3.44 (0.5 H, M, diastereomer B), 2.82 (1H, M), 2.65 (3H, M), 2.52-2. 45 (2H, M), 2.34-2. 28 (1H, M), 2.0-1. 76 (4H, M), 1.61 (2H, pent, J = 6.8 Hz), 1. 41-1. 18 (SH, M), 0.99-0. 71 (6H, M). M/Z = 486 [MH] + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39.7% | With potassium phosphate;(bis(tricyclohexyl)phosphine)palladium(II) dichloride; In water; toluene; at 100℃; for 24h; | EXAMPLE 114 3-butyl-2-methyl-6-[(3-pyridinylsulfonyl)amino]benzoic acid EXAMPLE 114A benzyl 3-butyl-2-methyl-6-[(3-pyridinylsulfonyl)amino]benzoate [0342] A mixture of Example 112A (115 mg, 0.25 mmol), K3PO4 (185 mg, 0.875 mmol), n-<strong>[4426-47-5]butylboronic acid</strong> (34 mg, 0.325-mmol), and bis(tricyclohexylphosphine)palladium dichloride (18 mg, 0.025 mmol) in toluene (4 mL) and water (0.2 mL) was purged with nitrogen and stirred at 100 C. for 24 hours. The mixture was then directly chromatographed on a silica gel column, eluting with 30% ethyl acetate/hexanes to provide the desired product (87 mg, 39.7%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; at 65℃; for 18h; | Example 8 Preparation of 3-(4-Butylphenyl)-2-(2-chlorophenyl)-5-methyl-6-(2,2,2-trifluoroethyl)-2,6-dihydropyrazolo[4,3-d]pyrimidin-7-one (8A-1): A mixture of 3-(4-bromophenyl)-2-(2-chlorophenyl)-5-methyl-6-(2,2,2-trifluoroethyl)-2,6-dihydropyrazolo[4,3-d]pyrimidin-7-one (4A-9, 48.4 mg, 0.1 mmol), 1-butane boronic acid (12 mg, 0.12 mmol), K2CO3 (41 mg, 0.3 mmol), PdCl2dppf.CH2Cl2 (8 mg, 0.01 mmol) in THF (2 ml) was heated at 65 C. for 18 h. The reaction mixture was cooled to room temperature, diluted with H2O, and extracted with EtOAc (2*). The combined extracts were washed with 0.5 M citric acid, saturated aqueous NaCl, dried, and concentrated under vacuum. The crude residue was purified on a Chromatotron using 1 mm plates and 25% EtOAc/hexanes as a solvent to give 8A-1 (16 mg): MS (m/z) 475.5 (M+H)+; 1H NMR (400MHz, CDCl3): delta 7.53-7.49 (m, 1H), 7.47-7.36 (m, 3H), 7.31 (d, J =8.3 Hz, 2H), 7.12 (d, J=8.3 Hz, 2H), 4.98-4.78 (br m, 2H), 2.60 (s, 3H), 2.56 (t, J=7.5 Hz, 2H), 1.6-1.5 (m, 2H), 1.36-1.27 (m, 2H), 0.89 (t, J=7.5 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; toluene; at 100℃; for 12h; | A mixture of 2-benzyl-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester (300 mg), n-<strong>[4426-47-5]butylboronic acid</strong> (340 mg), tetrakis(triphenylphosphine)palladium(0) (80 mg), potassium carbonate (280 mg), toluene (6 ml) and THF (3 ml) was stirred at 100C under a nitrogen atmosphere for 12 hrs. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine. The solvent was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-hexane:ethyl acetate=2:1) and crystallized from hexane to give the title compound (210 mg).1H-NMR (CDCl3) delta: 0.88 (3H, t, J=7.3 Hz), 1.14-1.66 (4H, m), 2.61 (2H, t, J=7.7 Hz), 3.18 (3H, s), 5.44 (2H, s), 6.94-7.06 (1H, m), 7.14-7.50 (11H, m), 8.47 (1H, d, J=8.4 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With cesium fluoride;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 80℃; for 10h; | Example 127 3-14- [3- (2-BENZOYL-4-BUTYL-PHENOXY)-BUTOXY]-2-METHYL-PHENYLL-PROPIONIC acid Step A 3- {4- [3- (2-Benzoyl-4-butyl-phenoxy)-butoxy]-2-methyl-phenyl}-propionic acid methyl ester; The compounds of 3- {4- [3- (2-benzoyl-4-bromo-phenoxy)-butoxy]-2- METHYL-PHENYL}-PROPIONIC acid methyl ester (0.128 g, 0.244 mmol) (Example 126, Step A), 77-BUTYLBORONIC acid (0.075 g, 0.736 mmol) and cesium fluoride (0.130 g, 0.856 mmol) are combined in 1,4-dioxane (6 mL) and purged with N2. The reaction is treated with 1, 1'-bis (diphenylphosphino) ferrocene palladium (II) chloride and CH2C12 complex (0.027 g, 0.037 mmol) and then heated in an oil bath at 80 C for 10 hours under N2. The reaction is cooled, and the solvent is removed in vacuo to afford crude product that is absorbed on silica gel and column purified using 10/1 hexanes/acetone to afford 0.066 g (54%) of the title compound. Rf= 0.26 (2/1 hexanes/acetone). IH NMR (400 MHz, CDC13) ; MS (ES+) INLZ mass calcd for C32H3805 502, found 503 (M + 1,100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In toluene; at 100℃; for 1 - 24h; | Method G Three equivalents of boronic acid or ester, six equivalents of K2CO3 and 0.3 equivalents of tetrakis (tripheynylphosphine) palladium are added to the appropriate bromo-substituted compound of formula III in toluene. The reaction is heated to 100C for 1-24h. The reaction is then quenched with CH2C12 and washed with water. The CH2C12 layer was dried (Na2S04) and evaporated in vacuo to give a solid or oily residue. The residue is then either recrystallised or purified by flash chromatography using EtOAc/hexanes or by preparative HPLC. Compound 132 Compound 132 was prepared using Method G employing compound 107 and n- <strong>[4426-47-5]butylboronic acid</strong>. 1H NMR (300 MHz, CDCl3): 8 0.89 (t, J 7.5 Hz, 3H), 1.23-1. 37 (m, 3H), 1.48-1. 56 (m, 2H), 2.59 (t, J 7.8 Hz, 2H), 3.12-3. 26 (m, 2H), 3.62-3. 69 (m, 1H), 3.83-3. 78 (m, 1H), 7.26- 7.35 (m, 3H), 7.62-7. 69 (m, 3H). MS m/z ( [M+H] +) 341 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In toluene at 90 - 118℃; for 3h; Inert atmosphere; Dean-Stark; | |
94% | In toluene for 8h; Dean-Stark; Reflux; Inert atmosphere; | |
In toluene refluxed in toluene; |
by method from A. B. Charette and H. Juteau, J. Am. Chem. Soc., 116, 2651 (1994); | ||
In toluene for 8h; Heating / reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; tricyclohexylphosphine;palladium diacetate; In water; toluene; at 100℃; for 2.58333h; | Ethyl (3-(2-bromo-4-chlorophenyl)-1-{1-[4-(trifluoromethyl) phenyl]butyl}-4,5,6,7- tetrahydro-1H-indol-7-yl) acetate (prepared using the procedures of example 1, steps 1 and 2 using 2-bromo-4-chloro-1-[(E)-2-nitrovinyl]benzene in place of [(E)-2- nitrovinyl] benzene in step 1) (41 mg, 0.068 mmol) was dissolved in toluene (2 ml) and water (1 ml) and n-<strong>[4426-47-5]butylboronic acid</strong> (9 mg, 0.088 mmol), K3P04 (51 mg, 0.24 mmol), tricyclohexylphosphine (2 mg, 0.007 mmol), and palladium acetate (2 mg, 0.007 mmol) added. The mixture was degassed for 5 min, then heated to 100C and stirred for 2 h 30 min. The reaction was then allowed to cool, then diluted with water and extracted twice with ethyl acetate. The combined organics were washed with brine, dried over sodium sulfate, concentrated in vacuo and purified by column chromatography (1-10% EtOAc/Hexanes) to give the desired ester (12 mg) as a colourless oil. This ester was hydrolysed following the procedure in Example 1 Step 3 to afford the desired acid; m/z (ES-) 544 (M-H(at)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 155℃; for 0.0833333h;Microwave irradiation; | EXAMPLE 73; 6-Butvl-3-r(1-ethvlpiperidin-3-vl)methvn-2-(2-methoxyphenvl)quinazolin-4(3H)-onetrifluoroacetate; OH[421 ] 6-Bromo-3-[(1 -ethylpiperidin-3-yl)methyl]-2-(2-methoxyphenyl)quinazolin-4(3H)-one(65 mg, 0.14 mmol) (Example 49, step 1), n-<strong>[4426-47-5]butylboronic acid</strong> (22 mg, 0.21 mmol), and Pd[P(Ph3)4]104(8 mg, 0.07 mmol) were dissolved in DMF (2 ml_) followed by addition of Na2CO3 (0.4 mL, 2 N).The mixture was degassed and subjected to microwave radiation at 155C for 5 min. The mixturewas filtered through a silica gel plug using EtOAc as eluent. The filtrate was concentrated underreduced pressure. The crude was purified using a Gilson reversed-phase HPLC system with agradient elution from 5% to 55% acetonitrile in water to afford 18.8 mg (24%) of the title product.1H NMR (300 MHz, CD3OD) 5 8.09 (d, 1 H), 7.75 (dd, 1 H), 7.59-7.66 (m, 2 ), 7.51-7.56 (m, 1 H),7.14-7.26 (m, 2 H), 4.31 (dd, 0.6 H), 4.18 (dd, 0.4 H), 3.88 (s, 3 H), 3.70 (dd, 0.6 H), 3.54 (dd, 0.4H), 3.38-3.49 (br, 2 H), 3.09 (m, 2 H), 2.41-2.84 (m, 4 H), 2.04-2.28 (br, 1 H), 1.81-1.95 (m, 1 H),1.01-1.78 (m, 10 H), 0.98 (t, 3 H); ES-MS m/z 434.3 (MH+); HPLC RT (min) 1.03. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; silver(l) oxide;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; at 80℃; for 20h; | Example 56; 5 mL of trifluoromethanesulfonic anhydride was added under ice cooling to a 50 mL pyridine solution of 5 g of the compound obtained in Example 39, and the system was stirred for 2 hours at the same temperature. After the reaction, water was added at the same temperature, and extraction was performed with ethyl acetate. The extracted organic layer was washed with saturated brine, dried with magnesium sulfate, and then subjected to reduced-pressure solvent distillation. The residue thus obtained was refined by silica gel column chromatography (25% ethyl acetate/ hexane) to obtain 6.24 g of 2-acetyl-4,5-dihydro-7-(trifluoromethanesulfonyloxy)naphtho[1,2-b]thiophene in the form of a yellow powder. A suspension of 1.0 g of the compound obtained above, 0.3 g of n-<strong>[4426-47-5]butylboronic acid</strong>, 0.19 g of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) dichloride, 1.1 g of potassium carbonate, and 1.5 g of silver oxide in 10 mL of tetrahydrofuran was stirred for 20 hours at 80C under nitrogen replacement. After the reaction, 15 mL of 30% aqueous hydrogen peroxide and 15 mL of a 10% sodium hydroxide aqueous solution were added under ice cooling, and extraction was performed with ethyl acetate. The extracted organic layer was washed with saturated brine, dried with magnesium sulfate, and then subjected to reduced-pressure solvent distillation. The residue thus obtained was refined by silica gel column chromatography (10% ethyl acetate/hexane) to obtain 0.18 g of 2-acetyl-4,5-dihydro-7-(n-butyl)naphtho[1,2-b]thiophene (Table 8) in the form of a yellow powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74.88% | With hydrogenchloride; In water; | 1.2 Preparation of Butyl Boronic Acid 18 To a 1-L, three-necked, round bottomed flask equipped with a magnetic stirrer and thermometer, was added 480 ml of ether, followed by 20 ml (176 mmol) of trimethylborate. The clear solution was cooled to -75 C. (internal temperature) and vigorously stirred, then 90 ml (176 mmol) of 1.95 M solution of butylmagnesium bromide in ether was added dropwise via cannula at such a rate that the internal temperature did not exceed -65 C. After the addition was completed, the resulting white slurry was stirred for an additional 2 hours at -75 C. under nitrogen. The cooling bath was then removed and the reaction mixture was allowed to warm to room temperature (between 1h and 2h are needed). Hydrolysis was carried out by the dropwise addition of 200 ml of a 10% aqueous solution of hydrochloric acid. The white precipitate was dissolved and the resulting clear biphasic mixture was stirred for 15 min, after which time, the two layers were separated. The aqueous layer was extracted with ether (2*100 ml), and the combined extracts dried over magnesium sulfate. After concentration of the ethereal solution under reduced pressure, the residual white solid was purified by recrystallization as follows: after dissolution in hot water (50 ml), the resulting biphasic solution was cooled to 0 C. to induce recrystallization of the boronic acid. The solid was collected on a medium fritted disk funnel and washed with 100 ml of hexanes and placed under vacuum for 60 min. A quantity of 13.6 g of the boronic acid 18 was produced as a white solid. Yield: 74.88%; m.p.=94-96 C. (lit. m.p.=95-97 C.) (Charette, A. B.; Juteau, H.; Lebel, H.; and Molinaro C. J. Am. Chem. Soc. 1998, 120, 11943-11952); Characterization: Nmr (1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With tin(II) pyrophosphate; In ethanol; water; at 140℃; for 0.0833333h;physiological saline; | Into a 5 ml siliconized serum vial are measured 1.0 mg of dimethyl glyoxime in 0.1 ml of ethanol, 5.0 mg of 1-butane boronic acid in 50 mul of ethanol, 0.3 ml of saturated aqueous potassium bromide, and 25 mul of saturated aqueous stannous pyrophosphate.Sodium pertechnetate in physiological saline (0.1 ml) is added to the vial which is heated at 1400C for 5 minutes yielding 59% of the title complex. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tin(II) pyrophosphate; In ethanol; water; at 140℃; for 0.0833333h;physiological saline; | Into a 5 ml siliconized serum vial are measured 1.0 mg of dimethyl glyoxime in 0.1 ml of ethanol, 5.0 mg of 1-butane boronic acid in 50 mul of ethanol, 0.3 ml of saturated aqueous sodium chloride and 25 mul of saturated stannous pyrophosphate.Sodium pertechnetate in physiological saline (0.1 ml) is added to the vial which is heated at 1400C for 5 minutes yielding 70% of the title complex. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In toluene; at 100℃; | 4-Bromo-2-fluoro-benzaldehyde {Tetrahedron 61 , 6590, 2005) (253 mg, 1.0 mmol), butaneboronic acid (165 mg, 1.6 mmol), potassium carbonate (1.0 mL, 2 M, 2.0 mmol), and toluene (2.0 mL) were combined in a vial and sparged with argon. Tetrakis(triphenylphosphine)palladium (58 mg, 0.05 mmol) was added, and the vial was sealed. The reaction was magnetically stirred at 100 C overnight. The cooled reaction mixture was extracted with ether (3 x 4 mL), and the combined extract was concentrated onto celite. The product was isolated by silica gel flash chromatography (EtOAc in hexanes, 0-15%). The product was collected as colorless oil. Yield 165 mg, 72%. |
72% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In toluene; at 100℃;Inert atmosphere; | 4-Butyl-2-fluoro-benzaldehyde 4-Bromo-2-fluoro-benzaldehyde (Tetrahedron 61, 6590, 2005) (253 mg, 1.0 mmol), butaneboronic acid (165 mg, 1.6 mmol), potassium carbonate (1.0 mL, 2 M, 2.0 mmol), and toluene (2.0 mL) were combined in a vial and sparged with argon. Tetrakis(triphenylphosphine)palladium (58 mg, 0.05 mmol) was added, and the vial was sealed. The reaction was magnetically stirred at 100 C. overnight. The cooled reaction mixture was extracted with ether (3*4 mL), and the combined extract was concentrated onto celite. The product was isolated by silica gel flash chromatography (EtOAc in hexanes, 0-15%). The product was collected as colorless oil. Yield 165 mg, 72%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In dichloromethane; at 42℃; for 1h;Inert atmosphere;Product distribution / selectivity; | Following an analogous procedure from Bundy, G. L.; Peterson, D. C; Cornette, J. C; Miller, W. L; Spilman, C. H.; Wilks, J. W. J. Med. Chem. 1983, 26, 1089-1099, to <n="31"/>a solution of <strong>[155206-00-1]bimatoprost</strong> (Cayman Chemicals 16820, Lot 188757; 679 mg, 1.63 mmol) in DCM (10.9 mL) was added butylboronic acid (187 mg, 1.84 mmol). After 1 hour at 42C, solvent was removed under reduced pressure and dried under high vacuum pump for 2 hours. Fresh DCM was added and stirred at 42C for another hour. Solvent was removed and dried under high vacuum pump for 1.5 hour. Fresh DCM was added again and stirred at 42C for 16 hours. Solvent was evaporated and dried in vacuum oven at 45C for 3 hours to give 904 mg (100%) of boronate b-1 as an oil, which was used directly in the next step without further purification.1H NMR (400 MHz, DMSO-cfe) delta 0.50 - 0.66 (m, 2 H), 0.76 - 0.91 (m, 3 H)1 0.98 (t, J=7.20 Hz, 3 H), 1.16 - 1.35 (m, 4 H), 1.52 (quin, J=7.39 Hz, 2 H), 1.57 - 1.71 (m, 2 H),1.74 (br. s., 1 H), 1.78 - 2.09 (m, 6 H), 2.08 - 2.23 (m, 2 H), 2.23 - 2.32 (m, 1 H), 2.52 - 2.65 (m, 2 H), 2.95 - 3.12 (m, 2 H), 3.79 - 3.93 (m, 1 H), 4.02 (s, 1 H), 4.25 (br. s., 1 H),4.75 (d, J=4.55 Hz, 1 H), 5.26 - 5.54 (m, 4 H)1 7.09 - 7.22 (m, 3 H), 7.26 (t, J=7.45 Hz, 2 H)1 7.62 - 7.82 (m, 1 H). |
In tert-butyl methyl ether; at 40℃; for 1h; | Methyltertbutyl ether (2800mL, l4vol.) was charged in a flask. <strong>[155206-00-1]Bimatoprost</strong> (200 g, 1 eq.) was added and the equipment was rinsed with methyltertbutyl ether (200 mL, 1 vol.). Butyl boronic acid (58.94 g, 1.13 eq.) was added to the resulting suspension in one portion, the equipment was rinsed with methyltertbutyl ether (200 mL, 1 vol.). The mixture was heated to 40C for 1 hour. The reaction was monitored by 1 H (0091) NMR till conversion >97%. (0092) The reaction mixture was cooled to 20C to 25C, clarified on a glass filter and washed with methyltertbutyl ether (200 mL, 1 vol.). The filtrate was charged in the 4L three-neck round bottomed flask, the equipment was rinsed with methyltertbutyl ether (100 mL, 0.5 vol.) and the media was heated at a temperature about 40C under vacuum for azeotropic distillation. Rinsing with methyltertbutyl ether and azeotropic distillation was continued till the water content of (Z)-7-[(lS,5R,6R,7R)-3-butyl-6-[((E,3S)-3- hydroxy-5 -phenyl-pent- 1 -enyl]-2,4-dioxa-3-borabicyclo[3.2.1 )octan-7-yl]-N-ethyl-hept- 5-enamide (compound (II)) was equal to or below 0.25%. Compound of formula (II) was obtained with quantitative yield (281.22 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With sodium carbonate; caesium carbonate;chloro(di-norbonylphosphino)(2?-dimethylamino-1,1?-biphenyl-2-yl)palladium(II); In toluene; at 105℃;Product distribution / selectivity; | Example 3: as Example 1, except that 318 mg of sodium carbonate (3 mmol) and 33 mg of cesium carbonate (0.3 mmol) were used in place of the sodium hydroxide solution. The solvent used was 5 ml of toluene. The yield was 96 %. |
94% | With potassium phosphate;chloro(di-norbonylphosphino)(2?-dimethylamino-1,1?-biphenyl-2-yl)palladium(II); In tetrahydrofuran; ISOPROPYLAMIDE; toluene; at 105℃;Product distribution / selectivity; | Example 2: as Example 1, except that 637 mg (3 mmol) of anhydrous potassium phosphate were used in place of the sodium hydroxide solution. Instead of dioxane, the solvent used was 5 ml of a mixture of dimethylacetamide, toluene and tetrahydrofuran (1:1:1). The yield was 94%. |
94% | With sodium hydroxide;chloro(di-norbonylphosphino)(2?-dimethylamino-1,1?-biphenyl-2-yl)palladium(II); In water; isopropyl alcohol; toluene; at 105℃;Product distribution / selectivity; | Example 4: as Example 1, except that the dioxane solvent was replaced by 5 ml of a mixture of toluene and isopropanol (1:1). 94% butylbenzene was obtained. |
93% | With sodium hydroxide;chloro(di-norbonylphosphino)(2?-dimethylamino-1,1?-biphenyl-2-yl)palladium(II); In 1,4-dioxane; water; at 105℃;Product distribution / selectivity; | Suzuki coupling of bromobenzene with n-<strong>[4426-47-5]butylboronic acid</strong> with catalysis by 2'-(dimethylamino)-2-biphenylylpalladium(II) chloride-dinorbornylphosphine complex (SK-CC01-A)With exclusion of air, 0.157 g of bromobenzene (1.0 mmol), 0.152 g of <strong>[4426-47-5]butylboronic acid</strong> (1.5 mmol), 5.6 mg of SK-CC01-A (0.01 mmol, 1 mol %) and 1 ml of 3N sodium hydroxide solution (3 mmol) in 5 ml of dioxane were heated to 105 C. with stirring until the conversion (according to GC) was complete. The mixture was allowed to cool, the reaction mixture was extracted with 4 ml of water and the organic phase was removed. Filtration through silica gel (eluent: ethyl acetate) afforded 0.125 g (0.93 mmol, 93%) of n-butylbenzene. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium carbonate; silver(l) oxide;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; at 80℃; for 40h; | Step 3-1 The compound (0.2 g) obtained in step 1-7, [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane complex (1:1) (0.011 g), <strong>[4426-47-5]butylboronic acid</strong> (0.050 g), silver(I) oxide (0.12 g), potassium carbonate (0.15 g) and tetrahydrofuran (1.6 ml) were mixed, and the mixture was stirred at 80 C. for 40 hr. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: hexane/ethyl acetate=8/2-6/4) to give the compound described in the above-mentioned scheme (0.13 g, 77%).1H-NMR (DMSO-D6) delta: 0.91 (t, 3H, J=7.7 Hz), 1.28-1.39 (m, 2H), 1.48 (s, 9H), 1.71-1.81 (m, 2H), 3.11 (t, 2H, J=7.7 Hz), 5.38 (s, 2H), 7.23 (s, 1H), 7.32-7.51 (m, 5H), 8.39 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium carbonate; silver(l) oxide;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; for 10h;Reflux; | Step 117-1 The compound (0.050 g) obtained in step 116-4, <strong>[4426-47-5]butylboronic acid</strong> (0.042 g), silver(I) oxide (0.071 g), potassium carbonate (0.084 g), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane complex (1:1) (0.008 g) and tetrahydrofuran (1.0 ml) were mixed, and the mixture was heated under reflux for 10 hr. Insoluble material was filtered off through celite, and saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added. The organic layer was separated from the mixture. The organic layer was washed twice with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the obtained residue was purified by thin layer chromatography (eluent: hexane/ethyl acetate=1/1) to give the compound described in the above-mentioned scheme (0.046 g, 77%).1H-NMR (CDCl3) delta: 1.00 (t, 3H, J=7.4 Hz), 1.45-1.53 (m, 2H), 1.79-1.87 (m, 2H), 3.18 (t, 2H, J=7.9 Hz), 4.08 (s, 3H), 6.92 (s, 1H), 8.38 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; In dichloromethane; water; at 20℃; for 10h; | General procedure: To a solution of benzoquinone (0.5 mmol, 1.0 equiv) and [Cp*RhCl2]2 (0.025 mmol, 5 mol%) in CH2Cl2 (2 mL) was added the boronic acid (0.75 mmol, 1.5 equiv), H2O (1 mL). Then the solution was stirred vigorously at r.t. for 10 h. Upon completion, the reaction was diluted with CH2Cl2 (3 mL) and washed with 5% NaHCO3. The layers were separated, and the aqueous layer was extracted with CH2Cl2 (3 × 4 mL), dried over Na2SO4, and was evaporated to give the residue. The residue was then purified by column chromatography on silica gel (EtOAc-PE, 1:10) to provide the corresponding product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With palladium diacetate; sodium carbonate; triphenylphosphine; In 1,2-dimethoxyethane; water; for 16h;Inert atmosphere; Reflux; | General procedure: To a mixture of 5'-O-tert-butyldimethylsilyl-2',3'-O-isopropylidene-6-iodouridine30 (6, 0.2620 g, 0.50 mmol), arylboronic acid (1.2-4.0 equiv), triphenylphosphine (0.0262 g, 0.10 mmol, 0.2 equiv), and palladium(II) acetate (0.0112 g, 0.05 mmol, 0.1 equiv) in toluene (5 mL) was added 2 M aqueous sodium carbonate solution (0.75 mL, 1.50 mmol, 3 equiv) at room temperature. The reaction system was filled with argon then the reaction mixture was heated at reflux temperature for 16 h. After cooling to room temperature, the solvent was removed under reduced pressure and the residue was partitioned between EtOAc and H2O. The organic layer was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography to give the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | To a 50 mL 3 -neck flask equipped with overhead stirring, a reflux condenser, a nitrogen inlet, and a thermocouple were added primary amine D-malate salt (3.00 g, 7.07 mmol), «-<strong>[4426-47-5]butylboronic acid</strong> (0.036 g, 0.353 mmol, 5 mol%), and -propyl acetate (30.0 ml, 10 vol). The reaction was heated to reflux over 15 min (bath temperature 110 C). After 7 hours, a distillation head was connected to the reaction flask. 15 mL of solvent was removed by distillation over 30 minutes to affect removal of water. The distillation head was then removed.After an additional 3 hours, the temperature was set to 70 C. At this time HPLC analysis showed 96% conversion of the malic acid salt to a 7:1.5:1 mixture of the amido acids and the succinimide. Hexamethyldisilazane (HMDS) (2.95 ml, 14.13 mmol, 2.0 equiv) was added (note: gas evolution and a mild exotherm were observed), followed by anhydrous zinc chloride (0.963 g, 7.07 mmol, 1.0 equiv) (note: a mild exotherm was observed). The temperature was maintained at 70 "C for 6 hours, after which HPLC analysis showed 98.2% conversion of the amides to the succinimide.The mixture was then allowed to cool to 50 C. 1 M aqueous hydrochloric acid (15 mL, 5 vol) was added over 5 minutes, forming a clear biphasic solution. The phases were cut at 50 C. Subsequently, the organics were washed with additional 1 M aqueous hydrochloric acid (6 mL, 2 vol), with the cut again performed at 50 C. Total aqueous losses were 3.1%, and the assay yield of succinimide in the organics was 85%.The organics were concentrated twice from ^-propyl acetate (15 mL, 5 vol) to remove water. The resulting solid was suspended in o-propyl acetate to a total volume of 15 mL. The mixture was warmed to 60 C to affect dissolution, then cooled to 45 C, at which point seed crystals (1 wt%) were added. The mixture was cooled to 22 C over 3 hours. Heptane (18 mL, 6 vol) was added over 6 hours. The mixture was cooled to 2 C over 4 hours, and the crystals were collected by filtration. The filter cake was washed with heptane (12 mL, 4 vol) and dried to constant weight by nitrogen flowthrough. 2.23 g (77% yield) of white plates were obtained with 94 wt % purity and 94.9 LCAP. Combined liquor losses were 3.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With tetrakis(triphenylphosphine) palladium(0); tri-tert-butyl phosphine; potassium carbonate; In water; toluene; at 85℃; for 24h;Inert atmosphere; | 4.3.1 3,6-di-n-butylcarbazole 1 A mixture of 3,6-dibromocarbazole (11.1 g, 34.3 mmol), n-<strong>[4426-47-5]butylboronic acid</strong> (8.41 g, 82.4 mmol), toluene (150 mL) and potassium carbonate (aq) (2 M, 50 mL) was deoxygenated with nitrogen for 30 min. Tetrakis(triphenylphosphine)palladium (0) (0.196 g, 0.170 mmol) and tri-tert-butylphosphine (0.208 g, 1.03 mmol) were added. The reaction mixture was stirred at 85 C for 24 h. After cooling to room temperature, water was added. The aqueous layer was extracted with toluene. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated invacuo. The crude material was purified by column chromatography on a silica gel (0:1-1:1 chloroform: hexane) to give 2 as a white solid (5.90 g, 62%). 1H-NMR (400 MHz, DMSO-d6) delta 10.90 (s, 1H), 8.85 (s, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 2.65 (t, J = 7.8 Hz, 4H), 1.60 (m, 4H), 1.30 (m, 4H), 0.85 (m, J = 7.4 Hz, 6H). C-NMR (400 MHz, CDCl3): delta 138.40, 134.05, 126.62, 123.64, 119.71, 110.43, 36.02, 34.79, 22.72, 12.38. EI-MS (M+m/z): Calcd. For C20H25N: 279.2, found: 279. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 160℃; for 0.0833333h;Microwave irradiation; Inert atmosphere; | Following the general procedure described above using <strong>[4426-47-5]butylboronic acid</strong> (2l) and benzoxazine 6 the title compound 7k was obtained (0.170 g, 55%) as an oil after purification by flash chromatography (5% EtOAc/hexane); Rf (10% EtOAc/petroleum ether 40-60 C) 0.40; numax(neat) 3390, 1499, 1259, 1104 cm-1; deltaH (600 MHz, CDCl3) 7.45-7.39 (4H, m, Ph), 7.35-7.33 (1H, m, Ph), 5.04 (1H, dd, J 9.0, 1.9 Hz, CHPh), 3.59 (1H, dd, J 11.9, 1.9 Hz, CH2CHPh), 3.55 (1H, bs, 1H, NH), 3.29 (1H, dd, J 11.9, 9.0 Hz, CH2CHPh), 2.63-2.61 (2H, m, PhCH2CH2CH2CH3), 2.20 (6H, s, Me), 2.11 (3H, s, Me), 1.47-1.42 (4H, m, PhCH2CH2CH2CH3), 0.98 (3H, t, J 7.0 Hz, PhCH2CH2CH2CH3); deltaC (75.5 MHz, CDCl3) 140.7, 139.9, 131.6, 128.4, 128.3, 127.9, 126.1, 125.3, 122.3, 119.0, 75.4, 48.6, 32.5, 29.7, 23.2, 15.3, 14.0, 12.6, 12.0; MS(EI), m/z: 309 (100, M+); HRMS (ESI+): [M+H]+, found 310.2171. C21H28NO requires 310.2165. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 90℃; for 3h;Inert atmosphere; Sealed tube; | Under An Argon Atmosphere, In 50mL Sealed Tube With A Stir Bar Was Added Sequentially Bis Propargyl Alcohol Carbonate If (0.2mmol, 108mg), N-Butyl Boronic Acid (0.8mmol, 82mg), Tetrahydrofuran (5mL) Was Dissolved , Tetrakis Triphenylphosphine Palladium (0.01mmol, 12mg), 90 C Reaction 3h, TLC Detection Reaction Was Completed; The Reaction Mixture Was Washed With Ethyl Acetate Into IOOmL Egg-Shaped Flask, An Appropriate Amount Of Neutral Alumina, Spin Dry, Neutral Alumina Column Chromatography To Give Orange-Red Solid 53mg, Yield 74% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 90℃; for 2.5h;Sealed tube; Inert atmosphere; | Under Argon In A Sealed Tube With Stirring 50mL Added Sequentially Double Propynol Carbonate 3 (0.2mmol, 100.9mg), N-Butyl Borate (0.8mmol, 82mg), Tetrahydrofuran (5mL) Was Dissolved, Was Added Tetrakistriphenylphosphine Palladium (0.01mmol, 12mg), 90 C At A Reaction 2.5h, TLC Detection Reaction Was Completed; The Reaction Mixture Was Washed With Ethyl Acetate Into IOOmL Egg-Shaped Flask, An Appropriate Amount Of Neutral Alumina , Spin Dry, Neutral Alumina Column Chromatography To Give A Dark Purple Solid56.Lmg, Yield 68%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | In nitromethane; for 2h;Inert atmosphere; Reflux; | alpha-Benzyldioxime (0.79 g, 3.3 mmol), CoCl2·6H2O (0.26 g, 1.1 mmol) and n-butylboronic acid (0.25 g, 2.42 mmol) were dissolved/suspended in dry nitromethane (20 ml) under argon. The stirred reaction mixture was refluxed for 2 h and then the solvent (10 ml) was partially distilled off. The reaction mixture was cooled to room temperature, and the dark-brown precipitate formed was filtered off. The product was isolated and purified as described above for the complex FeNx3(Bn-C4H9)2. Yield: 0.66 g (66%). Anal. Calc. for ?50?48N6CoO6B2: C, 66.01; H, 5.28; N, 9.24; Co, 6.49. Found: C, 66.04; H, 5.35; N, 9.29; Co, 6.50%. MS MALDI-TOF: m/z: 909 [M]+?. 1H NMR (CD2Cl2) delta (ppm): -0.60-0.05 (m, 4?, ?H2B), 0.49 (s, 6?, CH3), 0.55-0.87 (m, 8?, CH2CH2), 6.79 (br s, 12?, meta-Ph), 9.09 (br s, 6?, para-Ph), 10.36 (br s, 12?, ortho-Ph). 13C{1H} NMR (CD2Cl2) delta (ppm): -1.78 (br. s, ?H2B), 15.75 (s, CH3), 28.01 (s, 3-CH2), 32.66 (s, 2-CH2), 90.49 (s, ortho-Ph), 121.00 (s, para-Ph), 136.52 (s, meta-Ph). IR (cm-1, KBr): 858, 928, 941, 1041, 1184 nu(N-O); 1115 m nu(B-O), 1581 nu(C=N). UV-Vis (CH2Cl2): lambdamax/nm (epsilon * 10-3, mol-1 L cm-1): 259 (38), 271 (15), 296 (15), 328 (7.5), 390 (11), 462 (3.8), 502 (9.0). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | In nitromethane; for 1.5h;Reflux; Inert atmosphere; | alpha-Benzyldioxime (0.79 g, 3.3 mmol), solvato-complex [Fe(CH3CN)4Cl2] (0.32 g, 1.1 mmol) and n-butylboronic acid (0.22 g, 2.2 mmol) were dissolved/suspended in dry nitromethane (20 ml) under argon. The stirred reaction mixture was refluxed for 1.5 h and then the solvent (10 ml) was partially distilled off. The reaction mixture was cooled to room temperature and the orange precipitate was filtered off. The product was isolated and purified as described above for the complex FeNx3(Bn-C4H9)2. Yield: 0.20 g (20%). Anal. Calc. for ?50?48N6FeO6B2: C, 66.23; H, 5.30; N, 9.27; Fe, 6.18. Found: C, 66.10; H, 5.19; N, 9.11; Fe, 5.93%. MS MALDI-TOF: m/z: 906 [M]+?. 1H NMR (CD2Cl2) delta (ppm): 0.18 (t, J1H-1H = 7.2 Hz, 4H, ?H2B), 0.54 (t, J1H-1H = 6.6 Hz, 6H, CH3), 0.90-0.97 (m, 8H, CH2CH2), 7.15-7.24 (m, 24H, meta-Ph + para-Ph), 7.30-7.33 (m, 12H, ortho-Ph). 13C{1H} NMR (CD2Cl2) delta (ppm): 15.89 (br. s, ?H2B), 18.72 (s, CH3), 27.07, 28.29 (two s, CH2CH2), 129.57 (s, meta-Ph), 131.28 (s, para-Ph), 131.93 (s, ipso-Ph), 132.73 (s, ortho-Ph); 156.77 (s, C=N). IR (cm-1, KBr): 860, 887, 922, 935, 1001 nu(N-O); 1109 m nu(B-O), 1537 nu(C=N). UV-Vis (CH2Cl2): lambdamax/nm (epsilon * 10-3, mol-1 L cm-1): 254 (22), 281 (32), 300 (14), 329 (4.0), 431 (4.9), 459 (7.8), 487 (28). 57Fe Moessbauer spectrum (mm s-1): IS = 0.30, QS = 0.18. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 18h;Inert atmosphere; Sealed tube; | To a solution of compound 14 (120 mg, 0.31 mmol) in 1 mL of dioxane were added cesium carbonate (303 mg, 0.93 mmol) in H20 (0.5 mL), [Iota, - bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2) (15 mg, 0.019 mmol) and n-<strong>[4426-47-5]butylboronic acid</strong> (98 mu, 0.46 mmol) under N2. The reaction mixture was then heated at 90 C in a sealed vial for 18 h. It was cooled to room temperature and filtered through celite and washed with MeOH. The solvent was removed and the crude residue was purified using column chromatography (15% EtOAc/hexane) to obtain the compound 20a (97mg, 76%). To a solution of compound 20a (94 mg, 0.23 mmol) in 10 mL of MeOH were added zinc dust (149 mg, 2.30 mmol) and ammonium formate (145 mg, 2.30 mmol). The reaction mixture was stirred at room temperature for 10 min and filtered through celite. Then the solvent was evaporated and the residue was dissolved in water. This was extracted with EtOAc (3 x 20 mL), washed with water and dried over sodium sulfate. The solvent was removed under vacuum to obtain compound 21a (45 mg, 51%). To a solution of compound 21a (42 mg, 0.11 mmol) in 7 mL of anhydrous THF were added triethylamine (16 mu, 0.12 mmol) and valeryl chloride (13 mu, 0.11 mmol). The reaction mixture was re fluxed for 1 h. The solvent was then removed under vacuum, and the residue was dissolved in 5 mL of EtOH and NaOH (10 mg, 0.22 mmol) in 1 mL of H20 was added. The reaction mixture was refluxed for 18 h. The solvent was then removed under vacuum, and the residue was dissolved in EtOAc and washed with water. The EtOAc fraction was dried using sodium sulfate and evaporated and purified using column chromatography (20% EtOAc/hexane) to obtain the compound 22a (25 mg, 51%). Compound 22a (22 mg, 0.049 mmol) was dissolved in 1 mL of HC1 (4M in dioxane) and stirred at room temperature for 30 min. Then the solvent was removed under vacuum to obtain compound 23a (11 mg, 69%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 90℃; for 12h;Inert atmosphere; | General procedure for the synthesis of 4-Butylquinoline (Compound 26a): To a stirred solution of substrate Compound 25 (187 mg, 1.14 mmol) in 1,4-dioxane were added the <strong>[4426-47-5]butylboronic acid</strong> (234 mg, 2.28 mmol), Pd(PPh3)4 (37 mg, 0.032 mmol) and K2C03 (472 mg, 3.42 mmol). The resulting reaction mixture was stirred at 90 C under nitrogen atmosphere for 12 h. After completion of reaction (monitored by TLC), the reaction mixture was diluted with water and extracted with ethyl acetate (3 x 10 mL). The combined organic layer was dried over Na2S04 and concentrated under reduced pressure, crude material was purified by flash chromatography using CH2Cl2:MeOH as an eluent to obtain Compound 26a as a colorless liquid (100 mg, 73%). Colorless liquid (170 mg, 80%>). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 90℃; for 12h;Inert atmosphere; | General procedure for the synthesis of 3-Butylquinoline 1-oxide (Compound 13a): To a stirred solution of substrate Compound 1 1 (100 mg, 0.446 mmol) in 1 ,4-dioxane was added <strong>[4426-47-5]butylboronic acid</strong> (91 mg, 0.892 mmol), Pd(PPh3)4 (25 mg, 0.0228 mmol) and K2C03 (184 mg, 1.33 mmol). The resulting reaction mixture was stirred at 90 C under nitrogen atmosphere for 12 h. After completion of reaction (monitored by TLC), the reaction mixture was diluted with water and extracted with ethyl acetate (3 x 10 mL). The combined organic layer was dried over Na2S04 and concentrated under reduced pressure, crude material was purified by flash chromatography using CH2Cl2:MeOH as an eluent to obtain Compound 13a as a white solid (72 mg, 80%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In dichloromethane; at 45℃; for 20h;Inert atmosphere; | Latanoprost (61-1, 3.0 g, 6.94 mmol) in anhydrous dichloromethane (30 mL) was added n<strong>[4426-47-5]butylboronic acid</strong> (62-1, 0.778 g, 7.63 mmol). The mixture was heated at 45 C for 1 hour under a nitrogen atmosphere. Solvent was removed and the residue was dried in vacuo. Additional anhydrous dichloromethane was added and removed in vacuo for an additional 3 hours. Theresidue was further heated in anhydrous dichloromethane at 45 C for 16 hours and the solvent was removed under reduced pressure to obtain product 62-2 as a colorless oil (2.8 g, 80%). ?HNMR (400 MHz, CDC13) 7.33-7.25 (m, 2H), 7.25-7.17 (m, 3H), 5.52-5.37 (m, 2H), 5.01 (quintet, 1H), 4.33-4.28 (m, 1H), 4.08-4.04 (m, 1H), 3.68-3.60 (m, 1H), 2.86-2.76 (m, 1H), 2.73-2.63 (m, 1H), 2.31-2.21 (m, 4H), 2.16-2.09 (m, 2H), 1.96-1.91 (m, 1H), 1.82-1.47 (m, 9H), 1.43-1.22 (m,12H), 0.88 (t, 3H), 0.67 (t, 2H). |
In dichloromethane; at 45℃; for 22h;Inert atmosphere; | General procedure: [419] Example 9: (Z)-lsopropyl 7-((1 R,5S,6RJR)-3-butyl-7-((R)-3-hydroxy-5- phenylpentyl)-2,4-dioxa-3-borabicyclo[3.2.1]octan-6-yl)hept-5-enoate [420] To latanoprost (222.0 mg, 0.51 mmol) in anhydrous DCM (10 mL) was added n-<strong>[4426-47-5]butylboronic acid</strong> (60.1 mg, 0.59 mmol). The mixture was heated at 45C for 1 h under nitrogen atmosphere. Solvent was then removed and dried in vacuo for 2 h. Additional anhydrous DCM was added and dried in vacuo for further 3 h. The residue was again heated in anhydrous DCM (10 mL) at 45C for 16 h. Solvent was removed under reduced pressure, obtaining a clear colourless oil and used directly in the next step without further purification. H NMR (400 MHz, CDC ) delta (ppm): 7.28 - 7.17 (m, 2H), 7.17 - 7.03 (m, 3H), 5.49 - 5.27 (m, 2H), 4.93 (ddd, J = 15.2, 7.6, 4.9 Hz, 1 H), 4.28 - 4.13 (m, 1 H), 4.07 - 3.90 (m, 1 H), 3.65 - 3.46 (m, 1 H), 2.78 - 2.67 (m, 1 H), 2.67 - 2.41 (m, 1 H), 2.28 - 2.11 (m, 4H), 2.09 - 1.98 (m, 2H), 1.91 - 1.79 (m, 1 H), 1.79 - 1.53 (m, 7H), 1.53 - 1.38 (m, 3H), 1.38 - 1.07 (m, 12H), 0.89 - 0.75 (m, 3H), 0.64 - 0.52 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With 1,1'-bis(diphenylphosphino)ferrocenedichloropalladium(II)complex with dichloromethane; potassium carbonate; silver(l) oxide; In tetrahydrofuran; 1,4-dioxane; at 115℃; for 68h;Inert atmosphere; | A mixture of 6-chloro-N2-methyl-N4,N8-di-n-propylpyrimido [5 ,4-djpyrimidine-2,4,8-triamine (20) (400 mg, 1.29 mmol), <strong>[4426-47-5]butylboronic acid</strong> (223 mg, 2.19mmol), K2C03 (535 mg, 3.87 mmol), Ag20 (748 mg, 3.23 mmol) and Pd(dppf)C12xCH2C12(114 mg, 0.14 mmol) in THF (1.0 mL) and 1,4-dioxane (7.0 mL) was heated at 115 C for 20h under argon atmosphere. Butylboronic acid (120 mg, 1.18 mmol) and Pd(dppf)C12xCH2C12(60 mg, 0.07 mmol) were added and heating was continued for 48 h. The reaction mixturewas cooled and filtered through Celite. A saturated NaHCO3 solution (20 mL) was added to the filtrate and the resulting suspension was extracted with CH2C12 (2 x 20 mL). The combined organic extracts were washed with water (30 mL) and dried over solid anhydrous Na2SO4. After filtration, the solvent was removed and the residue was purified by flash column chromatography using gradient elution from PE/EtOAc (20:1) to PE/EtOAc (5:2) to give 6-n-butyl-N2-methyl-N4,N8-di-n-propyl-pyrimido[5,4-dlpyrimidine-2,4,8-triamine (117) (240 mg, 56%y). 400 MHz ?H NMR (CDC13, ppm): oe 6.78-6.65 (1H, m), 6.52-6.42 (1H, m),4.82-4.71 (1H, m), 3.57-3.50 (2H, m), 3.50-3.43 (2H, m), 2.99 (3H, d, J=5.1 Hz), 2.75-2.68 (2H, m), 1.83-1.65 (6H, m), 1.46-1.36 (2H, m), 1.01 (3H, t, J=7.3 Hz), 1.00 (3H, t, J=7.3Hz), 0.95 (3H, t, J=7.4 Hz). ESI-MS (m/z): 332 [M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; tri-t-butylphosphonium tetraphenylborate complex; In water; toluene; at 85℃; for 48h;Inert atmosphere; | A mixture of 4,7-dibromo-2,1,3-benzothiadiazole (4.08 g, 13.9 mmol), <strong>[4426-47-5]butylboronic acid</strong> (3.36 g, 33.0mmol), Pd(PPh3)4 (94 mg, 0.081 mmol), t-Bu3P·BPh4 (0.235 g, 0.450 mmol) and potassium carbonate(9.51 g, 68.8 mmol) in a solvent mixture of toluene (59 mL) and water (22 mL) was heated at 85 C andstirred for 2 days under nitrogen. After cooling, chloroform (200 mL) was added. Then, the solution waswashed with water (100 mL × 2) and sat. brine (100 mL). The obtained organic solution was dried overMgSO4. The solvent was removed on a rotary evaporator, and the residue was purified by silica gelcolumn chromatography using chloroform/hexane (1:6, v/v) as eluent to afford 2a as a light greenishyellow oil (2.92 g, 11.7 mmol, 85%); 1H NMR (400 MHz, CD3COCD3) 0.92 (t, J = 7.3 Hz, 6H), 1.34-1.44 (m, 4H), 1.72-1.79 (m, 4H), 3.06 (t, J = 7.6 Hz, 4H), 7.36 (s, 2H); C NMR (100 MHz, CD2Cl2)13.75, 22.65, 31.77, 31.91, 127.26, 133.45, 155.27. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; In dichloromethane; water; at 20℃; for 10h; | General procedure: To a solution of benzoquinone (0.5 mmol, 1.0 equiv) and [Cp*RhCl2]2 (0.025 mmol, 5 mol%) in CH2Cl2 (2 mL) was added the boronic acid (0.75 mmol, 1.5 equiv), H2O (1 mL). Then the solution was stirred vigorously at r.t. for 10 h. Upon completion, the reaction was diluted with CH2Cl2 (3 mL) and washed with 5% NaHCO3. The layers were separated, and the aqueous layer was extracted with CH2Cl2 (3 × 4 mL), dried over Na2SO4, and was evaporated to give the residue. The residue was then purified by column chromatography on silica gel (EtOAc-PE, 1:10) to provide the corresponding product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With [bis(acetoxy)iodo]benzene; water; triethylamine; In acetonitrile; at 20℃; for 0.166667h; | General procedure: To a stirred solution of appropriate organoboronic acids (2.0 mmol, 1.0 equiv.) and Et3N(4.0 mmol, 2.0 equiv.) in CH3CN(acetonitrile: 3mL, H2O: 44muL, 2.4mmol, 1.2 equiv.), DAIB (3.0 mmol, 1.5 equiv.), dissolved in acetonitrile (2mL) was added drop wise at room temperature and the mixture was allowed to stir for 10 minutes at that temperature. After completion of the reaction indicated by TLC, the reaction mixture was concentrated to a smaller volume and the crude mixture was directly purified by column chromatography over silica gel using pentane/Et2O aseluent. |
81% | With urea hydrogen peroxide adduct; In methanol; at 27 - 29℃; for 3h;Green chemistry; | General procedure: To a stirred solution of aryl/alkyl boronic acid (1 mmol) in methanol or acetonitrile solvent (1 ml) was added 1 equiv. of Urea-Hydrogen peroxide (UHP) (2.5 equiv for alkyl boronic acids) at room temperature and the progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with water and extracted with dichloromethane (DCM). The combined organic layer was dried over anhydrous sodium sulfate (Na2SO4), evaporated and subjected to silica gel column chromatography for further purification. |
63% | With sodium periodate; iodobenzene; In water; acetonitrile; at 80℃; for 8h; | General procedure: Toa stirred solution of appropriate organoboronic acids (2.0 mmol, 1.0 equiv.) and NaIO4 (4.0 mmol, 2.0 equiv.) in CH3CN-H2O(acetonitrile: 6 mL, H2O: 2 mL), iodobenzene (0.2 mmol, 10 mol%) was added and the mixture was heated at 80 0C for 8 h. After thecompletion of reaction, the reaction mixture was cooled and concentrated to a smaller volume and the crude mixture was directly purified by column chromatography over silica gelusing pentane/Et2O as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); monophosphine 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)ferrocene; In toluene; at 100℃; for 19h;Inert atmosphere; | Bis(dibenzylideneacetone)dipalladium(0) (11.5 mg, 2% mol) and 1,2,3,4,5-pentaphenyl-1-(di-tert-butylphosphino)ferrocene (29.1 mg, 1% mol) were added, under nitrogen flux, to a solution of 24 (500 mg, 2.04 mmol) in anhydrous toluene (5 ml), followed by K3PO4 (874 mg, 4.12 mmol) and n-butyl-boronic acid (251.8 mg, 2.47 mmol). The system was sealed, and the reaction mixture was stirred at 100 C for 19 h. After cooling to room temperature, toluene was removed by evaporation in vacuo to afford the crude product that was purified by flash column chromatography on silica gel (n-hexane/AcOEt 9:1) to give pure 25 (400 mg, yield: 88%). 1H NMR (200 MHz, CDCl3) delta (ppm): 0.93 (t, 3H, J = 7.3 Hz), 1.25-1.66 (m, 4H), 2.62-2.70 (m, 1H), 3.83 (s, 3H), 3.91 (s, 3H), 7.07 (t, 1H, J = 7.6 Hz), 7.35 (dd, 1H, J = 7.5 Hz, J = 1.8 Hz), 7.64 (dd, 1H, J = 7.5 Hz, J = 1.8 Hz); MS: m/z 222 (M+, 40), 223 ([M + 1]+, 100), 191 ([M - OCH3]+, 21). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃;Inert atmosphere; | General procedure: A solution of 7-iodo-3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amine (100 mg, 0.225 mmol), Pd(PPh3)4 (26 mg, 0.0225 mmol)and phenylboronic acid (33 mg, 0.27 mmol) in Ethylene glycol dimethyl ether (10 mL) was degassed with nitrogen for 5 min followed by addition of H2O (2 mL) and Na2CO3 (72 mg, 0.675 mmol) under continuous flow of nitrogen. The reaction mixture was stirredat 80 C for 3 h. The reaction mixture was cooled, filtered through Celite, diluted with water (45 mL), and extracted with (3 20 mL) ethyl acetate. The combined organic layers were dried over sodium sulfate and were concentrated in vacuo, the crude product was purified on a silica gel column using (20-50% ethyl acetate/petroleum ether) as eluent to afford 12a (71 mg, 80.1%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With palladium diacetate; sodium hydrogencarbonate; silver carbonate; p-benzoquinone; N-acetylglycine; In tetrahydrofuran; at 60℃; for 48h;Autoclave; | In 35mL reaction tube were added successively stirring, 4.5mg Pd(OAc)2(10mol%), corresponding pyridine aryl silane (0.2mmol), 30.6mg butyl boronic acid (0.6mmol), 4.6mg Ac-Gly-OH (20mol%), 21.8mg BQ (1.2equiv), 110.2mg Ag2CO3(2.0equiv)16.8mg NaHCO3(1.0equiv) and 1.0mL THF.And then supporting the Teflon plug closed reaction tube, placed in 60 magnetic stirrer reaction 48h.The reaction tube was removed from the heating means and cooling to room temperature, the reaction was diluted with ethyl acetate and suction filtered through Celite, and washing several times with ethyl acetate and the filtrate was concentrated using a rotary evaporator, the crude product obtained at the end of the reaction purification by silica gel plate to give the corresponding butylated isolated product weighed to determine the yield, and used for the qualitative detection of NMR and HRMS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With bis(acetylacetonate)nickel(II); potassium carbonate; In chlorobenzene; at 120℃; for 40h;Schlenk technique; | General procedure: Tryptanthrins (0.2 mmol), alkyl boric acids (1 mmol), Ni(acac)2 (0.03 mmol), potassiumcarbonate (0.4 mmol) and 2 mL chlorobenzene were added to a Schlenk tube. Then theresulting mixture was stirred at 120 oC for specific time until the reaction was completed.The reaction mixture was purified through flash column chromatography on a silica gel(Rf= 0.2-0.3, CH2Cl2; Eluent: Petroleum ether: dichloromethane= 1:20 to puredichloromethane) to yield the targeting products |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; at 100℃; for 4h; | A solution of methyl 3-bromo-2-methylbenzoate (500 mg, 2.2 mmol), n-<strong>[4426-47-5]butylboronic acid</strong> (890 mg, 8.7 mmol), Pd(PPh3)4 (252 mg, 0.22 mmol) and K2C03 (905 mg, 6.6mmol) in toluene (20 mL) was stirred at 100C for 4 h. After filtration, the filtrate was washed with brine (20 mL x 3), dried over Na2504 and concentrated. The residue was purified by HPLC to give methyl 3-butyl-2-methylbenzoate (120 mg, 27% yield) as colorless oil. LCMS (Method 5-95 AB, ESI): tR = 0.87 1, [M + Hj = 206.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With sodium carbonate; cesium fluoride; In 1,4-dioxane; at 110℃; for 5h;Schlenk technique; Inert atmosphere; | General procedure: A Schlenk tube (20 mL) was charged with a 1,3-indanedionemonotosylhydrazone (1) (0.5 mmol), an arylboronic acid (2)(0.75 mmol), K2CO3 (0.75 mmol) and CsF (0.25 mmol). The tubewas degassed for 30 s and then filled with argon. This operation wasrepeated three times. After 1,4-dioxane (5 mL) was added under anargon atmosphere, the resulting reaction mixture was stirred at 110 Cfor 5 h. After the completion of the reaction, the reaction mixturewas allowed to cool to room temperature. Ethyl acetate (5 mL) and asaturated solution of NaCl (5 mL) were added and the layers wereseparated. The aqueous phase was extracted three times with ethylacetate (3 × 5 mL). The organic layer was then dried over anhydrousMgSO4 and filtered and the solvent was removed under reducedpressure. The crude mixture was purified by chromatography on silicagel to yield the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | In diethyl ether; dichloromethane; at 20℃; for 5h;Molecular sieve; | The compound was prepared following a procedure reported in Organic Syntheses, Coll. Vol. 10, p. 613 (2004). To a solution of fluprostenol isopropyl ester (0.5 g, 1.0 mmol) in Et2O (3 ml) and DCM (1 ml), <strong>[4426-47-5]butylboronic acid</strong> (0.1 g, 1.0 mmol) was added. After stirring for a few minutes, some molecular sieves (4 A) were added. The mixture was stirred 5 h at room temperature. The reaction was controlled in TLC (Cy/AcOEt 7:3) using alumina. Because the reaction was not finished, a second aliquot of <strong>[4426-47-5]butylboronic acid</strong> (0.05 g, 0.5 mmol) was added and the reaction was stirred overnight. Then the mixture was filtered and concentrated affording the title compound (0.55 mg, Yield: 97%). 1H NMR (300 MHz, Chloroform-d) delta 7.49-7.35 (m, 1H), 7.32-7.00 (m, 3H), 5.81-5.53 (m, 2H), 5.53-5.33 (m, 2H), 5.10-4.90 (m, 1H), 4.61-4.46 (m, 1H), 4.34 (s, 1H), 4.16 (s, 1H), 4.08-3.82 (m, 2H), 2.58-2.38 (m, 1H), 2.38-2.19 (m, 3H), 2.18-2.04 (m, 2H), 2.06-1.93 (m, 1H), 1.92-1.56 (m, 4H), 1.50-1.06 (m, 9H), 1.03-0.75 (m, 4H), 0.74-0.65 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With palladium diacetate; cesium fluoride; tri tert-butylphosphoniumtetrafluoroborate; In water; toluene; for 1h;Reflux; | To a 200 mL reactor thoroughly dried and purged with argon, 1.79 g (5.01 mmol) of the compound (1) obtained in Synthesis Example 1,(10.0 mmol) of n-<strong>[4426-47-5]butylboronic acid</strong>, 0.06 g (0.26 mmol) of palladium acetate, 3.20 g (21.1 mmol) of cesium fluoride, 0.15 g of tri-tert-butylphosphonium tetrafluoroborate (0.51 mmol), 10 mL of toluene and 2 mL of distilled water were charged and heated under reflux in an oil bath for 1 hour. After the reaction solution was cooled to room temperature, the soluble matter was extracted with ethyl acetate, and the obtained fraction was washed with saturated brine and dried over anhydrous magnesium sulfate. After filtration of the magnesium sulfate, the filtrate was distilled off and the obtained residue was purified by silica gel column chromatography,3.29 g (yield 98%) of the target compound (hereinafter referred to as compound (2)) represented by the following formula (2) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In toluene for 1h; Inert atmosphere; Dean-Stark; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); In water; toluene; for 1h;Reflux; | 9 g of compound 6 (28.83 mmol), 5.88 g of n-butyl boronic acid (57.66 mmol), 1.06 g of Pd2(dba)3 (1.15 mmol), 0.95 g of s-phos (2.31 mmol), 30 g of K3PO4 (141.27 mmol) and 192 mL of toluene were added to a 500 mL round bottom flask, and the mixture was stirred under reflux for 1 hour. The reaction mixture was extracted with ethyl acetate and treated with MgSO4. The reaction mixture was purified by column chromatography to obtain 7.6 g of compound 4-1 (92%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium carbonate; caesium carbonate; In toluene; at 80℃; for 16h;Inert atmosphere; | n-Butylboronic acid (764 mg, 7.50 mmol), K2CO3 (2.08 g, 15.0 mmol) and Cs2CO3 (490 mg, 1.50 mmol) were suspended in toluene (20.0 mL) in a Schlenk tube and subjected to four freeze-pump-thaw cycles. Under an argon atmosphere, 2-bromothiophene (480 muL, 5.00 mmol), S-Phos (21.0 mg, 0.05 mmol) and palladium acetate (56.0 mg, 0.25 mmol) were added. The initially orange, quickly darkening suspension was heated to 80 C for 16 h, cooled to room temperature and opened to the atmosphere. Water (20 mL) was added and the whole was stirred for 1 h, during which time a dark emulsion formed. The phases were separated and the aqueous layer including the dark emulsion were extracted with CH2Cl2 (3 x 25 mL).The emulsion was removed during the phase separation in the last extraction step. The combined extracts were washed with saturated aqueous NaHCO3 (50 mL). The organic layer was treated with activated charcoal, dried (Na2SO4) and the solvent was removed in vacuo. Purification by column chromatography on silica gel (petrolether -> EtOAc:petrolether 1:19) yielded 80 mg of a slightly yellow liquid (11%). 1H NMR (300 MHz, DMSO-d6): delta 0.85 (t, J = 7.0 Hz, 3H), 1.20-1.45 (m, 2H), 1.49-1.60 (m, 2H), 2.75 (m,J = 7.0 Hz, 2H), 6.75 (dd, J = 6.9/2.2 Hz, 1H), 6.90 (t, J = 6.9 Hz, 1H), 7.05 (dd, J = 6.9/2.2, 1H,) ppm;13C NMR (75 MHz, DMSO- d6): delta 13.62, 21.55, 29.77, 33.46, 123.98, 125.29, 126.80, 128.26 ppm; IR (neat): nu 3422 (b), 2923 (m), 2853 (m), 1718 (m), 1416 (w), 1267 (s), 1206 (s), 1102 (s), 1023 (s), 1004(s), 826 (s), 730 (s), 688 (s), cm-1. The NMR data were in agreement with that reported.30a, 32 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In acetonitrile at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With tris-(dibenzylideneacetone)dipalladium(0); keYPhos; potassium carbonate In lithium hydroxide monohydrate; toluene at 60℃; for 12h; Inert atmosphere; Sealed tube; | |
84% | With potassium fluoride; palladium diacetate; 2-cyclohexyl-3-(diisopropylphosphino)-1-methyl-1H-indole In <i>tert</i>-butyl alcohol at 110℃; for 2h; Inert atmosphere; chemoselective reaction; |
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P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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