Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 135884-31-0 | MDL No. : | MFCD01318939 |
Formula : | C9H14BNO4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZWGMJLNXIVRFRJ-UHFFFAOYSA-N |
M.W : | 211.02 | Pubchem ID : | 2734321 |
Synonyms : |
|
Num. heavy atoms : | 15 |
Num. arom. heavy atoms : | 5 |
Fraction Csp3 : | 0.44 |
Num. rotatable bonds : | 4 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 56.46 |
TPSA : | 71.69 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) : | -6.97 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 0.87 |
Log Po/w (WLOGP) : | -0.05 |
Log Po/w (MLOGP) : | -0.25 |
Log Po/w (SILICOS-IT) : | -1.62 |
Consensus Log Po/w : | -0.21 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.68 |
Solubility : | 4.42 mg/ml ; 0.0209 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.96 |
Solubility : | 2.32 mg/ml ; 0.011 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -0.58 |
Solubility : | 55.5 mg/ml ; 0.263 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.48 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | 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 |
---|---|---|
73% | In ethanol at 25℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With potassium carbonate;tetrakis(triphenylphosphine)palladium (0); In ethanol; water; toluene; | EXAMPLE 94 2-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d] [1,3]oxazin-6-yl)-pyrrole-1-carboxylic acid tert-butyl ester A solution of 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d] [1,3]oxazin-2-one (0.87 g, 3.4 mmol) and tetrakis(triphenylphosphine)palladium(0) (96 mg, 0.08 mmol) in toluene (40 mL) was stirred under a flow of nitrogen for 25 min. To the solution was added sequentially 1-t-butoxycarbonylpyrrole-2-boronic acid (1.4 g, 7.0 mmol) in absolute ethanol (10 mL) and potassium carbonate (0.94 g, 7.0 mmol) in water (10 mL). The mixture was heated at 80 C. for 16 h and allowed to cool to rt. The reaction mixture was poured into aqueous saturated sodium bicarbonate solution (100 mL) and extracted with ethyl acetate (3*100 mL). The organic layers were combined, washed with water (100 mL) and brine (50 mL) and dried over magnesium sulfate. The solution was filtered, concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (30% ethyl acetate/hexane) to give the title compound as an off-white powder (0.7 g, 62%): mp 176 C. 1H NMR (CDCl3) delta1.40 (s, 9H), 1.73 (s, 6H), 6.17 (dd, 1H, J=1.8, 3.3 Hz), 6.22 (dd, 1H, J=3.3, 3.3 Hz), 6.77 (d, 1H, J=8.1 Hz), 7.13 (d, 1H, J=1.8 Hz), 7.23 (dd, 1H, J=1.8, 8.1 Hz), 7.33 (dd, 1H, J=1.8, 3.3 Hz), 7.69 (bs, 1H). MS ((-) ESI) m/z 341 [M-H]-. Anal. Calcd for C19H22N2O4: C, 66.65; H, 6.48; N, 8.18. Found: C, 65.46; H, 6.51; N, 7.74. |
58% | With potassium carbonate;tetrakis(triphenylphosphine)palladium (0); In ethanol; water; toluene; | A solution of 6-bromo-4,4-dimethyl-1,4-dihydro-benzo [d][1,3]oxazin-2-one (5.0 g, 20 mmol) and tetrakis(triphenylphosphine)palladium(0) (580 mg, 0.5 mmol) in toluene (200 mL) was stirred under a flow of nitrogen for 25 min. To the solution was added sequentially 1-tert-butoxycarbonylpyrrole-2-boronic acid (8.24 g, 39 mmol) in absolute ethanol (50 mL) and potassium carbonate (5.39 g, 39 mmol) in water (50 mL). The mixture was heated to 80 C. for 16 h and allowed to cool. The reaction mixture was poured into aqueous saturated sodium bicarbonate solution (200 mL) and extracted with ethyl acetate (3*200 mL). The organic layers were combined, washed with water (200 mL) and brine (100 mL) and dried over magnesium sulfate. The solution was filtered, concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (30% ethyl acetate/hexane) to give 2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo [d] [1,3] oxazin-6-yl)-pyrrole-1-carboxylic acid tert-butyl ester (4.0 g, 58%) as a tan solid, mp 172-173 C. |
58% | With potassium carbonate;tetrakis(triphenylphosphine)palladium (0); In ethanol; water; toluene; | EXAMPLE 17 tert-Butyl 2-cyano-5-(4,4-dimethyl-2-thioxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-1-carboxylate A solution of <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> (5.0 g, 20 mmol) and tetrakis(triphenylphosphine)palladium(0) (580 mg, 0.5 mmol) in toluene (200 mL) was stirred under a flow of nitrogen for 25 min. To the solution was added sequentially 1-tert-butoxycarbonylpyrrole-2-boronic acid (8.24 g, 39 mmol) in absolute ethanol (50 mL) and potassium carbonate (5.39 g, 39 mmol) in water (50 mL). The mixture was heated to 80 C. for 16 h and allowed to cool. The reaction mixture was poured into an aqueous saturated sodium bicarbonate solution (200 mL) and extracted with ethyl acetate (3*200 mL). The organic layers were combined, washed with water (200 mL) and brine (100 mL) and dried over magnesium sulfate. The solution was filtered, concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (30% ethyl acetate/hexane) to give 2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-pyrrole-1-carboxylic acid tert-butyl ester (4.0 g, 58%) as a tan solid, mp 172-173 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With potassium carbonate In 1,2-DME; water | 2 5-(2'-Oxo-2',3'-dihydrospiro[cyclohexane-1,3'-[3H]indol ]-5 '-yl-2-cyanopyrrole To a solution of 5'-bromo-spiro[cyclohexane-1,3'-indolin]-2'-one (3.4 g, 12 mmol) in 1,2-DME (100 mL) under a nitrogen atmosphere, was added tetrakis(triphenylphospine)palladium(0) (70 mg, 5 mol %). After 15 min, 2-borono-1H-pyrrole-1-carboxylic acid, 1-tert butyl ester (1.3 eq, 3.31 g, 15.6 mmol) and a solution of K2CO3 (2.3 eq, 3.83 g, 27.6 mmol) in water (5 mL) were added sequentially. The solution was heated to 80° C. for 3 h and allowed to cool. The reaction mixture was poured into water (200 mL) and extracted with EtOAc (2*100 mL). The organic layers were combined, washed with brine (150 mL) and dried over MgSO4. The solution was filtered, concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (eluding with 30% EtOAc/hexane) to give 2-(1',2'-dihydro-2'-oxospiro[cyclohexane-1,3'-[3H]indol ]-5 '-yl) -1H-pyrrole-1-carboxylic acid, tert-butyl ester (3.4 g, 76%) as a white powder, mp 177° C. 1H NMR (CDCl3;300 MHz) δ 1.38 (s, 9 H), 1.59-1.93 (r, 10H), 6.18 (m, 1H), 6.23 ('t', 1H, 3 Hz), 6.91 (d, 1H, J=8 Hz), 7.21 (d, 1H, J=8 Hz), 7.34 (m, 1H), 7.44 (s, 1H), 8.33 (br s, 1H, D2Oex). MS ((+)-APCI) m/z 367 [(M+H)+]. Anal. Calcd for C22H26N2O3: C, 72.11; H, 7.15; N, 7.64. Found: C, 71.7; H, 7.16; N, 7.5. |
76% | Stage #1: 5'-bromospiro[cyclohexane-1,3'-[3H]indol]-2'(1'H)-one In 1,2-dimethoxyethane for 0.25h; Nitrogen atmosphere; Stage #2: N-boc-2-pyrroleboronic acid With potassium carbonate In 1,2-dimethoxyethane; water at 80℃; for 3h; | To a solution of 5'-bromo-spiro[cyclohexane-1,3'-indolin]-2'-one (3.4 g, 12 mmol) in 1,2-DME (100 mL) under a nitrogen atmosphere was added tetrakis(triphenylphosphine)palladium(0) (70 mg, 5 mol %). After 15 min, 2-borono-1H-pyrrole-1-carboxylic acid, 1-tert butyl ester (1.3 eq, 3.31 g, 15.6 mmol) and a solution of K2CO3 (2.3 eq, 3.83 g, 27.6 mmol) in water (5 mL) were added sequentially. The solution was heated to 80° C. for 3 h and allowed to cool. The reaction mixture was poured into water (200 mL) and extracted with EtOAc (2×100 mL). The organic layers were combined, washed with brine (150 mL) and dried over MgSO4. The solution was filtered, concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (eluting with 30% EtOAc/hexane) to give 2-(1',2'-dihydro-2'-oxospiro[cyclohexane-1,3'-[3H]indol]-5'-yl)-1H-pyrrole-1-carboxylic acid, tert-butyl ester (3.4 g, 76%) as a white powder, mp 177° C. 1H NMR (CDCl3; 300 MHz) δ 1.38 (s, 9 H), 1.59-1.93 (m, 10 H), 6.18 (m, 1 H), 6.23 (‘t’, 1H, 3 Hz), 6.91 (d, 1 H, J=8 Hz), 7.21 (d, 1 H, J=8 Hz), 7.34 (m, 1 H), 7.44 (s, 1 H), 8.33 (br s, 1 H, D2Oex). MS ((+)-APCI) m/z 367 [(M+H)+]. Anal. Calcd for C22H26N2O3: C, 72.11; H, 7.15; N, 7.64. Found: C, 71.7; H, 7.16; N, 7.5. |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,2-dimethoxyethane at 80℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With potassium phosphate; tris(dibenzylideneacetone)dipalladium (0); tricyclohexylphosphine In 1,4-dioxane; water at 100℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium fluoride; tri-tert-butyl phosphine;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; In tetrahydrofuran; hexane; at 25℃; for 16h; | A vial was charged with <strong>[872141-26-9]5-bromo-7-fluoro-3,3-dimethyl-1,3-dihydro-2H-indol-2-one</strong> (1.0 g, 3.5 mmol), 1-tert-butoxycarbonyl-2-pyrroleboronic acid (1.12 g, 5.3 mmol), KF (0.67 g, 11.5 mmol), and Pd2(dba)3 monochloroform adduct (54 mg, 0.053 mmol) and placed under a nitrogen atmosphere. THF (8 mL) was added and the mixture was purged with nitrogen for 5 minutes. P(t-Bu)3 (10% wt. solution in hexane 0.370 mL, 0.126 mmol) was added via syringe and the mixture was stirred at 25 C. for 16 hours. The mixture was diluted with EtOAc and filtered through a plug of silica gel and concentrated. Purification by flash chromatography (500 mL 25% hexane/CH2Cl2, then 500 mL 100% CH2Cl2, then 500 mL 5% ethyl acetate/CH2Cl2) afforded the title compound (1.06 g, 88%) as colorless crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With sodium carbonate In water; acetonitrile at 150℃; for 0.25h; | 54.1 Step 1: Synthesis of 3-(2-Methoxy-phenyl)-5-(1H-pyrrol-2-yl)-1H-pyrrolo[2,3-b]pyridine To a Personal Chemistry microwave vial (2-5 ml size) were added 5-bromo-3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine (96 mg, 0.32 mmol), 1-N-(BOC)pyrrole-2-boronic acid (103 mg, 0.487 mmol) and 12 mg (5 mol %) of dichloro[1,1'-bis(diphenylphoshino)ferrocene]palladium(II) dichloromethane adduct, 1 ml of acetonitrile and 1 ml of a 2 M aqueous solution of sodium carbonate. The vial was sealed, evacuated and purged three times with nitrogen, then irradiated in a Personal Chemistry microwave reactor with a temperature setting of 150° C. for 15 minutes. Ethyl acetate (50 ml) was added, and the layers were separated. The aqueous fraction was extracted three times with ethyl acetate, and the combined organic fractions were washed with brine, dried (Na2SO4), filtered and concentrated. Purification by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes gave 28.1 mg (30%) of 3-(2-methoxy-phenyl)-5-(1H-pyrrol-2-yl)-1H-pyrrolo[2,3-b]pyridine as a tan solid. 1H-NMR (d6-DMSO) δ=11.78 (br.s, 1H), 11.32 (br. s, 1H), 8.56 (d, 1H), 8.20 (d, 1H), 7.66 (d, 1H), 7.59 (dd, 1H), 7.29 (dd, 1H), 7.12 (d, 1H), 7.07 (t, 1H), 6.83 (m, 1H), 6.49 (m, 1H), 6.10 (m, 1H), 3.82 (s, 3H); MS m/z: 290 [MH]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In Dimethyl ether; at 92℃; for 3h; | [00148] A mixture of 3A, 3-bromobenzene sulfonamide (0.1 g, 0.4 mmol) in DME (6 mL) and 2.0 M Na2CO3 (0.8 mL) was degassed by bubbling argon for 5 min.To this solution, Pd(PPl^)4 (28 mg, 0.025 mmol) was added. The mixture was heated at 92C for 3 h. After cooling to rt, it was extracted with EtOAc, and dried over Na2SO4. The crude product was purified by silica gel chromatography(hexanes/EtOAc = 3/1) to give 3B (293 mg, 90% yield) as a semi-solid. lH NMR (400 MHz, CDCl3) delta ppm 1.37 (s, 9 H) 4.88 (s, 2 H) 6.23 (m, 1 H) 7.36 (m, 1 H) 7.47 (t, J=7.69 Hz, 1 H) 7.55 (m, 1 H) 7.83 (d, J=8.35 Hz, 1 H) 7.90 (s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium carbonate In 1,2-dimethoxyethane at 97℃; for 3h; | 100.C [00356] To IOOB (3.48g, 11.8 mmol), 3A ( 3.0 g, 14.2 mmol) and sodium carbonate (23.7 mL, 2M, 47.4 mmol) in 1,2 dimethoxyethane (100 mL, flushed and degassed (3x) with nitrogen) was added Pd(PPh3^ (2.74 g, 2.37 mmol). The reaction was heated to 97 0C for 3 h. The catalyst was filtered over celite and washed with ethyl acetate. The organic layer was washed with water, brine and then dried over sodium sulfate. The solvent was removed and the crude residue was purified by flash column chromatography to give 4.11 g of product IOOC (91% yield). 1H NMR (400 MHz, Methanol-d4) δ ppm 1.09 (t, J=7.46 Hz, 3 H) 1.25 (s, 9 H) 2.87 - 3.04 (m, 2 H)6.24 - 6.44 (m, 2 H) 7.46 (dd, J=3.30, 1.83 Hz, 1 H) 8.24 (d, J=2.20 Hz, 1 H) 8.31 (d, j=8.56 Hz, 1 H) 8.45 (dd, J=8.80, 2.45 Hz, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With sodium carbonate In 1,2-dimethoxyethane for 4h; Heating / reflux; | 37 tert-butyl 2-{4-[(ethylsulfonyl)amino]phenyl}-1H-pyrrole-1-carboxylate A mixture of N-(4-bromophenyl)ethanesulfonamide (1.88 g, 7.2 mmol), N-methylpyrrole-2-carbonitrile-5-boronic acid (2.11 g, 10 mmol), tetrakis(triphenylphosphine) palladium(0) (0.42 g, 0.36 mmol), and sodium carbonate (3.2 g, 30 mmol in 60 mL of water) in dimethoxyethane (200 mL) was heated to reflux for 4 hours. The mixture was cooled and partitioned between saturated ammonium chloride and ethyl acetate. The combined organic layers were dried over magnesium sulfate, and concentrated. The residue was purified by silica gel Flash Chromatography (hexane/ethyl acetate; 7:3) to afford the title compound (2.4 g, 97%). HPLC purity component=95.8% at 210-370 nm; RT=9.8 min.; 85/15-5/95 (Ammon. Form. Buff. Ph=3.5/ACN+MeOH) for 10 min., hold 4 min the Xterra RP18 instrument, 3.5%, 150×4.6 mm, 1.2 mL/min. |
97% | With sodium carbonate In 1,2-dimethoxyethane; water for 4h; Heating / reflux; | 63 Example 63 Tert-butyl 2-{4-[(ethylsulfonyl)amino]phenyl}-1H-pyrrole-1-carboxylate A mixture of N-(4-bromophenyl)ethanesulfonamide (1.88 g, 7.2 mmol), N-methylpyrrole-2-carbonitrile-5-boronic acid (2.11 g, 10 mmol), tetrakis(triphenylphosphine) palladium(0) (0.42 g, 0.36 mmol), and sodium carbonate (3.2 g, 30 mmol in 60 mL of water) in dimethoxyethane (200 mL) was heated to reflux for 4 hours. The mixture was cooled and partitioned between saturated ammonium chloride and ethyl acetate. The combined organic layers were dried over magnesium sulfate, and concentrated. The residue was purified by silica gel Flash Chromatography (hexane/ethyl acetate; 7:3) to afford the title compound (2.4 g, 97%). HPLC purity component=95.8% at 210-370 nm; RT=9.8 min.; 85/15-5/95 (Ammon. Form. Buff. Ph=3.5/ACN+MeOH) for 10 min., hold 4 min the Xterra RP18 instrument, 3.5μ, 150*4.6 mm, 1.2 mL/min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; tris-(o-tolyl)phosphine;palladium diacetate; In N,N-dimethyl-formamide; | Similar to the procedure used to prepare Compound 32, Compound Ic was reacted with Compound 12a and Pd(OAc)2, P(?-tolyl)3, and 2N aqueous Na2CO3 in DMF to give Compound 23 as a clear, colorless oil. 1H NMR (400 MHz, CDCl3) 1.30 and 1.65 (rotamer A and B, two singlets, 9H), 4.42 (s, 2H), 6.25 (m, IH), 7.35-7.65 (complex, 5H); MS (ESI) m/z: 299 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
tris-(dibenzylideneacetone)dipalladium(0); | Example 118 tert-butyl 2-(2-[4-(3,4-diethoxyphenyl)-4-oxobutanoyl]amino}-6-phenylpyridin-4-yl)-1H-pyrrole-1-carboxylate Using N-(4-chloro-6-phenylpyridin-2-yl)-4-(3,4-diethoxyphenyl)-4-oxobutanamide obtained in Example 43-(3) (22.6 mg), tris(dibenzylideneacetone)dipalladium (1.1 mg), biphenyl-2-yl(dicyclohexyl)phosphine (1.8 mg), 1N aqueous potassium carbonate solution (0.1 mL) and [1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl] boronic acid (26.4 mg) as starting materials and in the same manner as in Example 117, tert-butyl 2-(2-[4-(3,4-diethoxyphenyl)-4-oxobutanoyl]amino}-6-phenylpyridin-4-yl)-1H-pyrrole-1-carboxylate (1.6 mg) was obtained. HPLC (220 nm) purity 84% (retention time 2.17 min) MS (ESI+, m/e) 584 (M+H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In not given hydrolysis of appropriate N-methyliminodiacetic acid boronate; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sodium hydroxide In tetrahydrofuran; water at 23℃; for 0.333333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate;palladium diacetate; triphenylphosphine; In 1,2-dimethoxyethane; water; at 100℃; for 22h;Inert atmosphere; | (4a) t-Butyl 2-(1,3-benzothiazol-2-yl)-1H-pyrrole-1-carboxylate Commercially available 1-(t-butoxycarbonyl)pyrrole-2-boronic acid (417 mg, 1.98 mmol) was dissolved in 1,2-dimethoxyethane (20 mL), and 2-chloro-1,3-benzothiazole (0.25 mL, 2.02 mmol), palladium (II) acetate (23.0 mg, 0.102 mmol), triphenylphosphine (105 mg, 0.400 mmol) and an aqueous potassium carbonate solution (3M, 1.3 mL, 0.433 mmol) were added, followed by stirring at 100C for 22 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (20 mL) and ethyl acetate (20 mL) were added, and the solution was separated. The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-20%) to afford the desired compound (490 mg, yield 82%) as a pale yellow oil. 1H-NMR (CDCl3, 400 MHz): delta 1.38 (9H, s), 6.30 (1H, t, J=3.1 Hz), 6.72 (1H, dd, J=2.0, 3.1 Hz), 7.39 (1H, ddd, J=1.2, 7.0, 8.0 Hz), 7.46 (1H, dd, J=2.0, 3.1 Hz), 7.49 (1H, ddd, J=1.2, 7.0, 8.0 Hz), 7.89 (1H, brd, J=8.0 Hz), 8.05 (1H, dt, J=1.2, 8.0 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium carbonate;palladium diacetate; triphenylphosphine; In 1,2-dimethoxyethane; water; at 100℃; for 14h;Inert atmosphere; | (5a) Ethyl 2-[1-(t-butoxycarbonyl)-1H-pyrrol-2-yl]-1,3-thiazole-5-carboxylate Commercially available 1-(t-butoxycarbonyl)pyrrole-2-boronic acid (850 mg, 4.3 mmol) was dissolved in 1,2-dimethoxyethane (30 mL), and commercially available <strong>[41731-83-3]ethyl 2-bromo-1,3-thiazole-5-carboxylate</strong> (0.50 mL, 3.35 mmol), palladium (II) acetate (38.0 mg, 0.169 mmol), triphenylphosphine (176 mg, 0.671 mmol) and an aqueous potassium carbonate solution (3M, 2.20 mL, 6.60 mmol) were added, followed by stirring at 100C for 14 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (30 mL) and ethyl acetate (40 mL) were added, and the solution was separated. The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-30%) to afford the desired compound (800 mg, yield 74%) as a yellow solid. 1H-NMR (CDCl3, 400 MHz): delta 1.39 (3H, t, J=7.0 Hz), 1.50 (9H, s), 4.38 (2H, q, J=7.0 Hz), 6.28 (1H, dd, J=3.1,3.5 Hz), 6.79 (1H, dd, J=2.0, 3.5 Hz), 7.43 (1H, dd, J=2.0, 3.1 Hz), 8.39 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium carbonate In 1,2-dimethoxyethane; water at 100℃; for 19h; Inert atmosphere; | 10.a (10a) t-Butyl 2-(5-methylpyrazin-2-yl]-1H-pyrrole-1-carboxylate Commercially available 2-bromo-5-methylpyrazine (260 mg, 1.50 mmol) and commercially available 1-(t-butoxycarbonyl)pyrrole-2-boronic acid (380 mg, 1.80 mmol) were dissolved in 1,2-dimethoxyethane (20 mL), and palladium (II) acetate (17.0 mg, 0.076 mmol), triphenylphosphine (79.0 mg, 0.301 mmol) and an aqueous potassium carbonate solution (1.5M, 2.0 mL, 3.00 mmol) were added, followed by stirring at 100°C for 19 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (20 mL) and ethyl acetate (20 mL) were added, and the solution was separated. The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-30%) to afford the desired compound (373 mg, yield 96%) as a yellow oil. 1H-NMR (CDCl3, 400 MHz): δ 1.41 (9H, s), 2.59 (3H, s), 6.28 (1H, m), 6.48 (1H, m), 7.41 (1H, m), 8.45 (1H, brs), 8.56 (1H, brs). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | An argon purged mixture of 7-iodotubericidine 1 (196 mg, 0.50 mmol), 1-7V- (Boc)-pyrrole-2-boronic acid (126 mg, 0.60 mmol), Na2CO3 (160 mg, 1.5 mmol), Pd(OAc)2 (5.6 mg, 0.025 mmol) and TPPTS (36 mg, 0.06 mmol) in water/MeCN (2:1, 3 ml) was stirred at 100 C for 3 h. After cooling the mixture was neutralized by the addition of aq HCl (IM), volatiles were removed in vacuo and the residue was purified by reverse phase chromatography (0- »100% MeOH in water) affording title compound 2k as greenish solid (127 mg, 77%). Compound was recrystallized from MeOH as white solid, after decolorization with active carbon. Mp 205-2070C. [alpha]D -80.5 (c 0.205, DMSO).1H NMR (500.0 MHz, DMSO-J6): 3.54 (ddd, lH,Jgem= 11.9,J5b,OH = 6.2,J5b,4= 3.9, H- 5'b); 3.62 (dd, lH,Jgem= 11.9,J5a,OH= 5.0,J5a,4= 3.9, H-5'a); 3.90 (td, lH,J4-,y = 3.9,J4>;3= 3.1, H-4'); 4.09 (ddd, IH, J3-,2-= 5.1,J3,OH = 4.8,J3-,4=3.1, H-3'); 4.41(ddd, lH,J2.OH=6.5,J2-1 =6.3,J2>;3=5.1,H-2');5.17(d, 1H,JOH,3=4.8, OH-3'); 5.20 (dd, 1H,JOH,5= 6.2, 5.0, OH-5'); 5.33 (d, 1H,JOH,2= 6.5, OH-5'); 6.09 (d, IH, Jvchi = 6.3, H-I'); 6.13 (ddd, IH, J3,4 = 3.3, J3>;NH = 2.4, J3j5 = 1.5, H- 3-pyrr); 6.16 (ddd, IH, J4,3 = 3.3, J4,5 = 2.7, J4;NH = 2.4, H-4-pyrr); 6.32 (bs, 2H, NH2); 6.85 (td, IH, J5,4 =J5,NH = 2.7, J5>;3 = 1.5, H-5-pyrr); 7.43 (s, IH, H-6); 8.12 (s, IH, H-2); 11.14 (bs, IH, NH-pyrr). 13C NMR (125.7 MHz, DMSO-^6): 62.00 (CH2-5'); 70.92 (CH-3'); 74.11 (CH-2'); 85.30 (CH-4'); 87.20 (CH-I '); 101.09 (C-4a); 107.34 (CH-3-pyrr); 108.68 (C-5); 109.06 (CH-4-pyrr); 118.77 (CH-5-pyrr); 120.55 (CH-6); 124.69 (C-2-pyrr); 150.35 (C-7a); 151.98 (CH-2); 157.62 (C-4). MS (ESI) m/z 332 (M+H), 354 (M+Na). HRMS (ESI) for C15H18N5O4 [M+H] calcd: 332.1353; found: 332.1354. Anal. Calcd for C15H17N5O4-1Z3H2O: C, 53.41; H, 5.28; N, 20.76. Found: C, 53.32; H, 5.16; N, 20.57. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42.6% | With sodium carbonate;trans-bis(triphenylphosphine)palladium dichloride; In 1,4-dioxane; at 100℃; for 1h; | To a suspension of methyl 6-chloro-5 -nitronicotinate (0.108 g, 0.499 mmol), l-Boc-pyrrole-2- boronic acid (0.210 g, 0.997 mmol), and trans-Dichlorobis(triphenylphosphine)palladium (II) (0.350 g, 0.499 mmol) in Dioxane (Volume: 2.3 mL) was added 2M Sodium carbonate (0.798 mL, 1.596 mmol) at 23 0C. The reaction was stirred at 100 0C for 1 hr. The resulting suspension was filtered and rinsed with dioxane and H2O. The filtrate was diluted with EtOAc (20 mL) and the layers were separated. The organic phase was washed with saturated NaHCpsi3 and brine, dried over MgSO4, filtered, rinsed with EtOAc, and dried in vacuo. The resulting crude material was purified via medium pressure chromatography using a gradient eluant Of CH2Cl2ZMeOH. The appropriate fractions were combined and concentrated via rotary evaporation to provide methyl 6-(l -(tert-butoxycarbonyl)- IH- pyrrol-2-yl)-5 -nitronicotinate (0.0738 g, 0.212 mmol, 42.6 percent yield) as an orange gummy solid. 1H NMR (400 MHz, DMSO-J6) delta ppm 1.32 (s, 9 H) 3.96 (s, 3 H) 6.41 (t, J=3.28 Hz, 1 H) 6.65 (dd, J=3.28, 1.77 Hz, 1 H) 7.50 (dd, J=3.28, 1.77 Hz, 1 H) 8.82 (d, J=I.77 Hz, 1 H) 9.33 (d, J=I.77 Hz, 1 H). ESI-MS: m/z 348.2 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.1% | Stage #1: 8-bromo-2'-deoxyguanosine; N-boc-2-pyrroleboronic acid With tri(sulfophenyl)-phosphine; palladium diacetate; sodium carbonate In water; acetonitrile at 80℃; for 4h; Inert atmosphere; Stage #2: With hydrogenchloride In water; acetonitrile at 0 - 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate In water; N,N-dimethyl-formamide at 90℃; for 4h; Inert atmosphere; | 8-(6-(lH-pyrrol-2-yl)benzo [d] [1,3] dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H- purin-6-amine [DZ3-29].; 1 -N-Boc-pyrrole-2-boronic acid (18.5 mg, 0.0877 mmol) was added to PU-H71 (30 mg, 0.0585 mmol) and NaHC03 (14.7 mg, 0.1755 mmol). DMF (1 mL) was added and the reaction mixture was evacuated and back filled with nitrogen. This was repeated four times then nitrogen was bubbled through the reaction mixture for 10 minutes. Then H20 (0.1 mL) and Pd(PPh3)2Cl2 (4 mg, 0.00584 mmol) were added and the reaction mixture was heated under nitrogen at 90°C for 4 h. DMF was removed under reduced pressure and to the resulting residue was added CH2C12 (1.5 mL) and TFA (0.3 mL). The mixture was stirred for 5 h at rt, then solvent was removed under reduced pressure and the resulting residue was purified by preparatory TLC (hexane:CH2Cl2:EtOAc:MeOH-NH3 (7N), 4:9:2: 1) to give 5.8 mg (22%) of DZ3-29. 1H NMR (500 MHz, CDCl3/MeOH-<¾) δ 8.17 (s, 1H), 7.04 (s, 1H), 7.01 (s, 1H), 6.88 (m, 1H), 6.27 (m, 1H), 6.21 (m, 1H), 6.03 (s, 2H), 4.17 (t, 7= 6.8 Hz, 2H), 3.29 (septet, J= 6.6 Hz, 1H), 2.80 (t, J= 6.7 Hz, 2H), 2.15 (m, 2H), 1.41 (d, J= 6.6 Hz, 6H); HRMS (ESI) m/z [M+H]+ calcd. for C22H26N702S, 452.1869; found 452.1872; HPLC: method A ¾ = 6.13, method B Rt = 6.43. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate In 1,2-dimethoxyethane; water at 80℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water at 95℃; for 4h; Inert atmosphere; | 15.1 15.1. tert-butyl 2-(1H-indazol-5-yl)-1H-pyrrole-1-carboxylate Into a 250 mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed sodium carbonate (1.08 g, 10.1 mmol), water (20 mL), ethylene glycol dimethyl ether (100 mL), 5-bromo-1H-indazole (1.00 g, 5.08 mmol), [1-[(tert- butoxy)carbonyl]-1H-pyrrol-2-yl]boronic acid (1.29 g, 6.09 mmol) and Pd(PPh3)4 (586 mg, 0.51 mmol). The solution was stirred for 4 h at 95°C in an oil bath and was diluted with 50 mL of water after cooling. The solution was extracted twice with 50 mL of dichloromethane and the combined organic layers were concentrated to dryness. The residue was purified over a silica gel column with ethyl acetate/petroleum ether (1 :10). This resulted in 1 g (70%) of tert-butyl 2-(1H-indazol-5-yl)-1H-pyrrole-1-carboxylate as yellow oil. |
50% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate In 1,2-dimethoxyethane; water at 80℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; at 80℃; for 12h;Inert atmosphere; | To a solution of <strong>[105309-59-9]tetrakis(4-bromophenyl)methane</strong> (0.6360 g,1 mmol) and N-(tert-butoxycarbonyl)-pyrrol-2-ylboronic acid(1.0128 g, 4.8 mmol) in 30 mL of THF was added 10 mL of a saturatedaqueous solution of potassium carbonate, and then degassedby bubbling nitrogen gas for 15 min. After adding Pd(PPh3)4 (57 mg,0.05 mmol) under a nitrogen atmosphere, the reaction mixturewasstirred at 80 C for 12 h, and then cooled to room temperature. Theresulting mixture was extracted with ethyl acetate three times. Thecombined organic layer was washed with deionized water anddried over sodium sulfate. After concentration under reducedpressure, the residual oil was purified by column chromatographyusing n-hexane: ethyl acetate (30: 1) as the eluent to give thedesired product as a light yellow solid in 81% yield. 1H NMR(400 MHz, DMSO-d6, d): 7.35 (t, J 2.0 Hz, 4 H), 7.30 (d, J 8.0 Hz,8 H), 7.26 (d, J 8.0 Hz, 8 H), 6.27 (s, 8 H), 1.29 (s, 36 H). 13C NMR(600 MHz, CDCl3, d): 149.92, 145.93, 134.96, 132.37, 130.58, 128.67,123.22, 115.03, 110.98, 84.10, 64.85, 28.05. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; at 80℃; for 12h;Inert atmosphere; | TNPPwas synthesized by the reaction of 1,3,5-tri(4-bromophenyl)benzene and N-(tert-butoxycarbonyl)-pyrrol-2-ylboronic acid accordingto the same method. 1H NMR (400 MHz, DMSO-d6, d): 7.90(s,3H), 7.75(d, J8.0Hz,6H),7.53 (d, J8.0Hz,6H),7.44 (s, 3H), 6.32(s, 6 H), 1.47 (s, 18 H). 13C NMR (600 MHz, CDCl3, d): 149.79, 142.52,140.26, 135.31, 134.09, 126.92, 125.44, 123.19, 115.08, 111.10, 110.39,84.14, 28.10. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 3h;Inert atmosphere; Darkness; | A nitrogen purged mixture of 5 (200mg, 1.01mmol), N-Boc-2-pyrroleboronic acid (321mg, 1.52mmol), K2CO3 (279mg, 2.02mmol) and Pd(Ph3)4 (58.4mg, 0.05mmol) in DME:/ H2O 4:1 (5.5mL) was stirred at 100C for 3h in the dark. The mixture was diluted with CH2Cl2 and washed with aqueous NH4Cl. The aqueous phase was re-extracted with CH2Cl2 and the combined organic extracts were dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography (hexane:diethyl ether 6:4) afforded 6i (84%) as a light yellow solid; mp 136C; 1H NMR (CDCl3) delta 12.00 (1H, br s); 7.95 (1H, d, J=8.1Hz); 7.45 (1H, m); 7.27-7.16 (2H, m); 6.51-6.43 (2H, m); 6.33 (1H, m); 1.18 (9H, s). Anal. Calcd for C16H17N3O2: C, 67.83; H, 6.05; N, 14.83. Found: C, 67.99; H, 6.00; N, 14.97. |
84% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In Dimethyl ether; water; at 100℃; for 3h;Inert atmosphere; Darkness; | A mixture of <strong>[143468-13-7]6-bromo-1H-pyrrolo[2,3-b]pyridine</strong> (200 mg, 1.01 mmol), N-Bocpyrrole-2-boronic acid (321 mg, 1.52 mmol), K2C03 (279 mg, 2.02 mmol) and Pd(PPh3)4 (58.4 mg, 0.05 mmol) in DME/H20 4:1 (5.5 ml) which had been previously purged with nitrogen was stirred at 100C for 3 h in the dark. The mixture was then diluted with DCM and washed with saturated aqueous NH4C1. The aqueous phase was extracted back with DCM and the combined organic extracts were driedover Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (Hexane/Et20: 3/2) afforded the desired adduct as a light yellow solid.Yield: 84%.mp: 136C.H NMR (300 MHz CDC13), 8: 12.00 (1H, bs); 7.95 (1H, d, J = 8.1 Hz); 7.45 (1H, m);7.27-7.16 (2H, m); 6.51-6.43 (2H, m); 6.33 (1H, m); 1.18 (9H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dimethyl sulfoxide; toluene Dean-Stark; Reflux; Inert atmosphere; Sealed tube; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32%; 26% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In ethanol; water; toluene; at 90.0℃; for 23h;Inert atmosphere; Sealed tube; | A 20-mL sealed tube was charged with 2,4-dichloro-6,7-dihydro-5H- cyclopenta[Z?]pyridine (0.250 g, 1.33 mmol), l-Boc-pyrrole-2-boronic acid (0.308 g, 1.46 mmol), tetrakis(triphenylphosphine)palladium(0) (0.076 g, 0.066 mmol), and CS2CO3 (1.30 g, 3.99 mmol). Toluene (8 ml), EtOH (2 ml) and water (4 ml) were added. The resulting mixture was stirred under Ar at 90 C for 23 h. After cooling to room temperature, the reaction solution was diluted with water (5 mL) and ethyl acetate (60 mL). The aqueous layer was separated and the organic layer was washed with saturated sodium chloride (5 mL) then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (100:0 to 75:250) as eluent to afford tert-butyl 2-(4-chloro-6,7-dihydro-5H-cyclopenta[^]pyridin-2-yl)- lH-pyrrole-l-carboxylate (0.138 g, 32%) as a yellow oil. MW = 318.80. ]H NMR (CDC13, 500 MHz) delta 7.33 (dd, / = 3.5, 2.0 Hz, 1H), 7.17 (s, 1H), 6.37 (dd, / = 3.0, 2.0 Hz, 1H), 6.21 (t, J = 3.5 Hz, 1H), 3.09 (t, J = 7.5 Hz, 2H), 3.04 (t, J = 7.5 Hz, 2H), 2.17 (quin, J = 7.5 Hz, 2H), 1.38 (s, 9H). MS: ESI+, m/z 319 [M+H]+ and 4-chloro-2-(lH-pyrrol-2-yl)-6,7-dihydro- 5H-cyclopenta[fr]pyridine (0.077 g, 26%) as an off-white solid. MW = 218.68. ]H NMR (CDCI3, 500 MHz) delta 9.63 (br s, 1H), 7.30 (s, 1H), 6.87-6.85 (m, 1H), 6.65-6.62 (m, 1H), 6.29-6.25 (m, 1H), 3.01 (t, / = 7.5 Hz, 2H), 2.96 (t, 7 = 7.5 Hz, 2H), 2.13 (quin, / = 7.5 Hz, 2H); ESI MS m/z 218 [M]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31%; 4% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In methanol; toluene; for 24h;Inert atmosphere; Reflux; | General procedure: To a stirred solution of the corresponding aniline (1 mmol),Cs2CO3 (2 mmol), and Pd(PPh3)4 (5 mol%) in toluene (20mL) at reflux and under nitrogen atmosphere, a solution ofN-Boc-pyrrol-2-yl boronic acid17 (1 mmol) in a mixture oftoluene (10 mL) and MeOH (3 mL) was added over 7 h. Themixture was stirred at reflux for 17 h, cooled, and the MeOHwas removed under reduced pressure. To the resultanttoluene suspension H2O (30 mL) was added, and the layerswere separated. The water layer was extracted with CH2Cl2(3 × 25 mL; or EtOAc for compound 5), the combinedorganic extracts were washed with H2O (30 mL), dried overMgSO4, filtered, and the solvent was evaporated underreduced pressure. The residue was purified by columnchromatography on silica gel using a suitable eluent asindicated below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate In methanol; toluene for 24h; Inert atmosphere; Reflux; | General procedure: To a stirred solution of the corresponding aniline (1 mmol),Cs2CO3 (2 mmol), and Pd(PPh3)4 (5 mol%) in toluene (20mL) at reflux and under nitrogen atmosphere, a solution ofN-Boc-pyrrol-2-yl boronic acid17 (1 mmol) in a mixture oftoluene (10 mL) and MeOH (3 mL) was added over 7 h. Themixture was stirred at reflux for 17 h, cooled, and the MeOHwas removed under reduced pressure. To the resultanttoluene suspension H2O (30 mL) was added, and the layerswere separated. The water layer was extracted with CH2Cl2(3 × 25 mL; or EtOAc for compound 5), the combinedorganic extracts were washed with H2O (30 mL), dried overMgSO4, filtered, and the solvent was evaporated underreduced pressure. The residue was purified by columnchromatography on silica gel using a suitable eluent asindicated below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate In methanol; toluene for 24h; Inert atmosphere; Reflux; | General procedure: To a stirred solution of the corresponding aniline (1 mmol),Cs2CO3 (2 mmol), and Pd(PPh3)4 (5 mol%) in toluene (20mL) at reflux and under nitrogen atmosphere, a solution ofN-Boc-pyrrol-2-yl boronic acid17 (1 mmol) in a mixture oftoluene (10 mL) and MeOH (3 mL) was added over 7 h. Themixture was stirred at reflux for 17 h, cooled, and the MeOHwas removed under reduced pressure. To the resultanttoluene suspension H2O (30 mL) was added, and the layerswere separated. The water layer was extracted with CH2Cl2(3 × 25 mL; or EtOAc for compound 5), the combinedorganic extracts were washed with H2O (30 mL), dried overMgSO4, filtered, and the solvent was evaporated underreduced pressure. The residue was purified by columnchromatography on silica gel using a suitable eluent asindicated below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In methanol; toluene; for 24h;Inert atmosphere; Reflux; | General procedure: To a stirred solution of the corresponding aniline (1 mmol),Cs2CO3 (2 mmol), and Pd(PPh3)4 (5 molpercent) in toluene (20mL) at reflux and under nitrogen atmosphere, a solution ofN-Boc-pyrrol-2-yl boronic acid17 (1 mmol) in a mixture oftoluene (10 mL) and MeOH (3 mL) was added over 7 h. Themixture was stirred at reflux for 17 h, cooled, and the MeOHwas removed under reduced pressure. To the resultanttoluene suspension H2O (30 mL) was added, and the layerswere separated. The water layer was extracted with CH2Cl2(3 × 25 mL; or EtOAc for compound 5), the combinedorganic extracts were washed with H2O (30 mL), dried overMgSO4, filtered, and the solvent was evaporated underreduced pressure. The residue was purified by columnchromatography on silica gel using a suitable eluent asindicated below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In methanol; toluene; for 24h;Inert atmosphere; Reflux; | General procedure: To a stirred solution of the corresponding aniline (1 mmol),Cs2CO3 (2 mmol), and Pd(PPh3)4 (5 mol%) in toluene (20mL) at reflux and under nitrogen atmosphere, a solution ofN-Boc-pyrrol-2-yl boronic acid17 (1 mmol) in a mixture oftoluene (10 mL) and MeOH (3 mL) was added over 7 h. Themixture was stirred at reflux for 17 h, cooled, and the MeOHwas removed under reduced pressure. To the resultanttoluene suspension H2O (30 mL) was added, and the layerswere separated. The water layer was extracted with CH2Cl2(3 × 25 mL; or EtOAc for compound 5), the combinedorganic extracts were washed with H2O (30 mL), dried overMgSO4, filtered, and the solvent was evaporated underreduced pressure. The residue was purified by columnchromatography on silica gel using a suitable eluent asindicated below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 56 mg 2: 36 mg | With [(t-Bu)3PH]BF4; palladium diacetate; sodium hydroxide In butan-1-ol at 80℃; for 2h; Inert atmosphere; Glovebox; Overall yield = 96 %; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38.3% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 95℃; for 2h; | To a solution of <strong>[644985-24-0]4-bromo-2,3-difluoro-benzaldehyde</strong> (4.3 g, 19.5 mmol, 1.0 eq) in dioxane (50 mL) was added boronic acid B (4.11 g, 19.5 mmol, 1.0 eq), Pd(dppf)Cl2CH2Cl2 (1.7 g, 1.95 mmol, 0.1 eq), Na2C03 (6.2 g, 58.5 mmol, 3.0 eq) and H20 (10 mL) . The mixture was stirred at 95 C for 2 h and allowed cool to rt. The reaction mixture was extracted with EtOAc. The organic layer was dried over Na2S04 and evaporated to give the crude product which was subject to flash chromatography (PE/EA = 5/1-2/1, v/v) to afford 2-(2,3-difluoro- 4-formyl-phenyl)-pyrrole-l-carbo l (2.3 g, 38.3%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 95℃; for 4h; Inert atmosphere; | 176 To a solution of 4-bromo-2,5-difluoro-benzoic acid methyl ester (3.23 g, 12.93 mmol, 1 eq) and N-boc-2- pyrroleboronic acid (3.0 g, 14.22 mmol, 1.1 eq) in dioxane (60 mL) and water (15 mL) was added Pd(PPli3)4 (747 mg, 0.647 mmol, 0.05 eq) and Na2C03 (4.12 g, 38.79 mmol, 3 eq). The mixture was stirred at 95 °C for 4 h under nitrogen. The mixture was allowed to cool to rt. The solvent was removed in vacuo and the residue was diluted with EA and water. The organic layer was separated and the aqueous layer was extracted with EA. The combined organic layers were dried and concentrated. The residue was purified by flash chromatography on a silica gel column (EA/PE = 1/40, v/v) to give 2-(2,5-difluoro-4-methoxycarbonyl-phenyl)-pyrrole-l - carboxylic acid tert-butyl ester (3.0 g, 69%) as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trans-bis(triphenylphosphine)palladium dichloride; potassium carbonate; In water; N,N-dimethyl-formamide; at 80℃; for 7.0h;Inert atmosphere; | General procedure: To a solution of o---dibromobenzenes, N---Boc---pyrrole---2---boronic acid 2 and 1.0 M K2CO3aq. in DMF was added PdCl2(PPh3)2 (20%/mol) under a nitrogen atmosphere. Theresulting mixture was heated at 80 C for 7 h. After cooling to room temperature, themixture was extracted with a mixture of EtOAc/hexane (v/v = 1:4). The organic layerwas washed with water and brine, and then dried over Na2SO4. After removal solvent,the residue was purified by silica gel column chromatography and recrystallization todi(N---Boc---pyrrol---2---yl---benzenes). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | General procedure: 3-Bromo-4-iodopyridine (1.0 g, 3.5 mmol) and 2 (3.71 g, 17.6 mmol) was placed in theflask under an argon atmosphere, and then toluene (75 ml), EtOH (25 ml) and 2.0 MK2CO3 aq. (33 ml) was added. The resulting solution was degassed by bubbling for 15min with argon and then Pd(PPh3)4 (203 mg, 0.17 mmol) was added. The reactionmixture was heated at 90 C for 24 h. After cooling to room temperature, water wasadded. The mixture was extracted with EtOAc and the combined organic layer wasdried over Na2SO4. After removal of the solvent, the residue was purified by silica gelcolumn chromatography (EtOAc:hexane = 1:2) to give di-tert-butyl2,2'-(pyridine-3,4-diyl)bis(1H-pyrrole-1-carboxylate) as colorless oil. Yield: 78% (1.1 g,2.7 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: 2,3-dibromopyridine; N-boc-2-pyrroleboronic acid With potassium carbonate In ethanol; water; toluene for 0.25h; Inert atmosphere; Stage #2: With tetrakis(triphenylphosphine) palladium(0) at 90℃; for 24h; | Synthesis of di-tert-butyl 2,2'-(pyridine-2,3-diyl)bis(1H-pyrrole-1-carboxylate) General procedure: 2,3-Dibromopyridine (0.40 g, 1.7 mmol) and 2 (1.8 g, 8.4 mmol) was placed in the flaskunder an argon atmosphere, and then toluene (36 ml), EtOH (12 ml) and 2.0 M K2CO3aq. (16 ml) was added. The resulting solution was degassed by bubbling for 15 minwith argon and then Pd(PPh3)4 (97 mg, 0.084 mmol) was added. The reaction mixturewas heated at 90 C for 24 h. After cooling to room temperature, water was added. The mixture was extracted with EtOAc and the separated organic layer was dried overNa2SO4. After removal of the solvent, the residue was purified by silica gel columnchromatography (EtOAc:hexane = 1:3) to give di-tert-butyl2,2'-(pyridine-2,3-diyl)bis(1H-pyrrole-1-carboxylate) as yellow oil. Yield: 88% (0.61 g,1.5 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 95℃; for 3.5h; | (1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)boronic acid (0.625 g, 2.96 mmol), sodium carbonate (1.05 g, 9.87 mmol) and Pd(PPh3)4 (0.285 g, 0.247 mmol) were loaded in a flask and then DME (50 mL), water (10 mL) and <strong>[60811-18-9]4-bromo-1-chloro-2-fluorobenzene</strong> (0.300 mL, 2.47 mmol) were added. The reaction mixture was stirred at 95C for 3h30. Water and dichloromethane were added and the layers were separated. The aqueous layer was extracted with dichloromethane and the organic layers were dried and concentrated. The crude was purified via biotage column chromatography (cyclohexane/dichloromethane 100/0 to 90/10) to give the title compound (600 mg, 82% yield) H NMR (500 MHz, CDCI3) ppm = 7.38-7.34 (m, 2H), 7.15 (dd, J = 10.0, 2.0 Hz, 1 H), 7.11-7.08 (m, 1 H), 6.24-6.20 (m, 2H), 1.43 (s, 9H). LC - MS (ESI, m/z. method K) Rt = 1.67 min - 196/198 (M-Boc+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With O4P(3-)*3K(1+)*5H2O; tris(1-adamantyl)phosphine; {2-[((acetyl-kappaO)amino)phenyl-kappaC](tri-1-adamantylphosphine)palladium}(p-toluenesulfonate); In tetrahydrofuran; butan-1-ol; at 20℃; for 5h; | To a mixture of <strong>[13223-25-1]2-<strong>[13223-25-1]chloro-4,6-dimethoxypyrimidine</strong></strong> (87 mg, 0.50 mmol, 1 equiv), N-Boc2-pyrroleboronic acid (116 mg, 0.55 mmol, 1.1 equiv), and K3P04?5H20 (0.33 g, 1.1 mmol, 2.2equiv) was added n-butanol (400 jtL) then a THF stock solution of 3 and PAd3 (100 jtL, 0.25j.tmol of Pd/PAd3). The mixture was stirred at room temperature for 5 h. The reaction mixturewas diluted with ethyl acetate then extracted with water. The combine organic layers wereevaporated and the crude product was purified by flash chromatography. After drying, 147 mg (96%) of 33 was obtained as a colorless oil.?H NMR (501 MHz, CDC13) 7.33 (dd, J= 3.1, 1.7 Hz, 1H), 6.77 (dd, J= 3.4, 1.7 Hz, 1H), 6.26 (t, J 3.3 Hz, 1H), 5.95 (s, 1H), 3.97 (s, 6H), 1.48 (s, 9H).?3C{?H} NMR (126 MHz, CDC13)oe 171.0, 159.4, 149.0, 133.0, 124.8, 117.9, 110.5, 87.6, 83.6,54.0, 27.7.HRMS (ESI) mlz calculated for C,5H19N304 (M+1) 306.1448, found 306.1431. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With 1,2,3-trimethoxybenzene; O4P(3-)*3K(1+)*5H2O; tris(1-adamantyl)phosphine; {2-[((acetyl-kappaO)amino)phenyl-kappaC](tri-1-adamantylphosphine)palladium}(p-toluenesulfonate); In tetrahydrofuran; at 100℃; for 5h;Inert atmosphere; | To a mixture of glibenclamide (247 mg, 0.50 mmol, 1 equiv), N-Boc-pyrroleboronic acid (127 mg, 0.60 mmol, 1.2 equiv), 1,3,5-trimethyoxybenzene (84 mg, 0.50 mmol, 1 equiv) as internal standard, and K3P045H20 (0.36 g, 1.2 mmol, 2.4 equiv) was added a THF stocksolution of 3 and PAd3 (2 mL in THF, 5 imol of Pd/PAd3). The mixture was stirred at 100 C for 5 h. The crude NMR yield was 65 % versus the internal standard. The reaction mixture was diluted with ethyl acetate then extracted with water. The combine organic layers were evaporated and the crude product was purified by flash chromatography and preparative HPLC. After drying, 116 mg (37 %) of 16 was obtained as a white solid.1H NMR (501 MHz, CDC13) 8.13 (d, J 2.4 Hz, 1H), 7.83 (t, J= 5.8 Hz, 1H), 7.78 (d, J= 8.3Hz, 2H), 7.43 -7.31 (m, 3H), 7.26 (dd, J= 3.3, 1.8 Hz, 1H), 6.86 (d, J 8.5 Hz, 1H), 6.37 (d, J= 7.9 Hz, 1H), 6.14 (t, J- 3.3 Hz, 1H), 6.11 (dd, J= 3.3, 1.8 Hz, 1H), 3.75 (s, 3H), 3.69 (q, J=6.6 Hz, 2H), 3.56-3.47 (m, 1H), 2.96 (t, J= 6.9 Hz, 2H), 1.80-1.72 (m, 2H), 1.64-1.46 (m, 4H),1.34 (s, 9H), 1.30- 1.03 (m, 4H).?3C{?H} NMR (126 MHz, CDC13) 165.2, 156.6, 150.1, 149.2, 146.3, 137.7, 133.8, 133.6,133.0, 129.9, 127.7, 127.2, 122.6,120.3, 114.7, 110.6, 110.6, 83.7, 56.0, 49.2, 40.5, 35.7, 33.0,27.8, 25.4, 24.6.HRMS (ESI) m/z calculated for C32H40N407S (M+1) 625.2691, found 625.2700. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With O4P(3-)*3K(1+)*5H2O; tris(1-adamantyl)phosphine; {2-[((acetyl-kappaO)amino)phenyl-kappaC](tri-1-adamantylphosphine)palladium}(p-toluenesulfonate); In tetrahydrofuran; at 70℃; for 5h; | To a mixture of <strong>[32601-86-8]<strong>[32601-86-8]2-chloro-3-methylquinoxalin</strong>e</strong> (89 mg, 0.50 mmol, 1 equiv), N-Boc-2- pyrroleboronic acid (158 mg, 0.75 mmol, 1.5 equiv), and K3P045H20 (0.45 g, 1.5 mmol, 3 equiv) was added THF (400 iL) then a THF stock solution of 3 and PAd3 (100 .iL, 0.25 imol of Pd/PAd3). The mixture was stirred at 70 C for 5 h. The reaction mixture was diluted with ethylacetate then extracted with water. The combine organic layers were evaporated and the crude product was purified by flash chromatography. After drying, 148 mg (96 %) of 30 was obtained as a white solid.1H NMR (501 MHz, CDC13) 8.09 - 7.98 (m, 2H), 7.74 - 7.63 (m, 2H), 7.43 (dd, J 3.4, 1.7 Hz, 1H), 6.44 (dd, J= 3.3, 1.7 Hz, 1H), 6.33 (t, J= 3.4 Hz, 1H), 2.56 (s, 3H), 1.17 (s, 9H).3C{1H} NMR (126 MHz, CDC13) oe 154.5, 149.6, 148.6, 141.2, 140.3, 130.7, 129.8, 129.1,129.0, 128.3, 122.5, 115.6, 111.4, 84.2, 27.4, 23.0.HRIVIS (ESI) mlz calculated for C18H19N302 (M+1) 310.1550, found 310.1552. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; cesium fluoride; In N,N-dimethyl-formamide; at 20 - 60℃; for 3h;Inert atmosphere; | General procedure: 18 (138.5mg, 0.47mmol) was added to a solution of boronic acid (304.5mg, 1.44mmol), cesium fluoride (303mg, 1.99mmol), and PdCl2(dppf) (81.2mg, 0.10mmol) in dry DMF (5mL) at room temperature under argon. The reaction mixture was heated at 60C for 3h, then neutralized with ammonium chloride, and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography (silica gel, AcOEt/n-hexane=1:4) to give 23 (129mg, 72%). Compounds 22 and 24 were synthesized similarly from compounds 14 and 21, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With tetrakis(triphenylphosphine) palladium(0); water; sodium carbonate In N,N-dimethyl-formamide at 130℃; for 6h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane for 48h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; bis(dibenzylideneacetone)-palladium(0); CyJohnPhos; In ethanol; water;Inert atmosphere; Reflux; | 4-Iodo-1,2-dimethoxybenzene (5; 16.7 g, 63.3 mmol) was dissolved in EtOH (63 mL), Boc-pyrroleboronic acid (4; 20.0 g, 94.8 mmol, 1.5 equiv) was added to the solution followed by the addition of an aqueous solution of K2CO3 (17.5 g, 126.8 mmol, 2 equiv; in 63 mL H2O). Under a constant flow of N2, CyJohnPhos (378 mg, 2 mol%) was added followed by Pd(dba)2 (364 mg, 1 mol%). The reaction mixture was vigorously stirred and heated under reflux for 4-5 h. The reaction mixture was cooled to r.t. and extracted with hexane (3 x 100 mL). The organic layer was dried over Na2SO4 and evaporated. To the residue (contains aryl iodide, Boc-pyrrole and product ~1:1:1) was added freshly prepared (from Na and MeOH) NaOMe solution (~1 M in MeOH, 3-5 equiv) and the mixture was left overnight. The reaction mixture was diluted with H2O and extracted with Et2O (3 x 100 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, and evaporated. The residue was triturated with hexane and filtered off to give pure enough compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60 mg | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; at 105℃; for 3.0h;Inert atmosphere; | To a solution of 4-chloro-2- (methylthio) -6- (trifluoromethyl) pyrimidine (94.9mg, 0.42mmol) , 1- (tert-butoxycarbonyl) -1H-pyrrol-2-ylboronic acid (87mg, 0.42mmol) , Pd (pph3) 4 (24.1mg, 0.02mmol) and Na2CO3 (1ml) in DME (3ml) under nitrogen was heated 105 for 3h. The mixture was cooled to RT and extracted with DCM (3*20 mL) . The organic layer was separated, dried over Na2SO4, filtered and concentrated. The crude product was purified by Prep. TLC to obtain the product (60mg) as a white solid. Mass (m/z) : 260.04 [M+H] +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium phosphate; (DPEPhos)Ni(mesityl)Br; water; In 1,4-dioxane; benzene; at 25℃; for 16h;Inert atmosphere; Sealed tube; | General procedure: Unless otherwise specified, under an inert atmosphere C1 (12.7mg, 0.016 mmol, 2 mol %), aryl halide (0.8 mmol), boronic acid(1.6 mmol), and K3PO4 (679 mg, 3.2 mmol) were added to anoven-dried 4 dram vial containing a magnetic stir bar. 1,4-Dioxane (1.3 mL) and benzene (700 muL) were added, the vial wassealed with a screwcap featuring a PTFE/silicone septum andwas removed from the glovebox. Degassed water (86 muL) wasadded via a gas-tight syringe. The reaction mixture was magneticallystirred for 16 h at room temperature. Note: On severaloccasions the base became clumpy and stuck to the bottom ofthe reaction vial; in these cases it was noted that reactions weremore successful if efficient stirring was maintained. After 16 h,the reaction mixture was taken up in EtOAc (ca. 10 mL) andextracted with distilled water (3 × 10 mL). The organic layer wasdried over anhydrous Na2SO4, filtered, and concentrated withthe aid of a rotary evaporator. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With palladium diacetate; caesium carbonate; In 1,4-dioxane; for 3h;Heating; | Ethyl 2-bromo-4-chloroquinoline-3-carboxylate (1.0 g) and (1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)boronic acid(0.6 g) is dissolved in an appropriate amount of 1,4-dioxane,Cesium carbonate (4.0 g) and palladium acetate (360 mg) were added thereto. The reaction solution was stirred at high temperature for 3 hours. After the reaction, the reaction mixture was poured into ice water and extracted with ethyl acetate (100 mL×2). The combined organic layers were washed with brine, dried over anhydrous sodium sulfateThe residue was purified by column chromatography (EtOAc: PET = 1: 30) to give the product as a colorless oil (64% yield). |
55% | With palladium diacetate; caesium carbonate; In 1,4-dioxane; for 3h; | Ethyl 2-bromo-4-chloroquinoline-3-carboxylate (1.0 g) and (1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)boronic acid were weighed(0.6 g) was dissolved in an appropriate amount of 1,4-dioxane, and cesium carbonate (4.0 g) and palladium acetate (360 mg) were added thereto. The reaction solution was stirred at high temperature for 3 hours. After the reaction was completed, the reaction solution was poured into ice water and extracted with ethyl acetate (100 mL×2). The combined organic phase was washed with brine, dried over anhydrous sodiumThe organic phase is concentrated.The residue is subjected to column chromatography to obtain the product asColorless oil (55% yield). |
53% | With palladium diacetate; caesium carbonate; In 1,4-dioxane; water; at 75℃; for 3h; | Weigh 2-<strong>[1379615-56-1]ethyl 2-bromo-4-chloroquinoline-3-carboxylate</strong> (3.2 mmol) and(1-(tert-Butoxycarbonyl)-1H-pyrrol-2-yl)boronic acid (3.3 mmol) was dissolved in 1,4-dioxane (15 mL) and water (6 mL).Cesium carbonate (6.5 mmol) and palladium acetate (0.3 mmol) were added thereto.The reaction was stirred at 75 C for 3 hours.After the reaction was completed, the reaction solution was poured into ice water and extracted with ethyl acetate (100 mL×2).The combined organic layers were washed with brine, dried over anhydrous sodium sulfateThe residue was purified by column chromatography (EtOAc: PET = 1: 30)(53% yield). |
53% | With palladium diacetate; caesium carbonate; In 1,4-dioxane; at 75℃; for 3h; | Ethyl 2-bromo-4-chloroquinoline-3-carboxylate (1.1 g, 3.2 mmol) and (1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)boronic acid (0.69 g, 3.3 mmol) Soluble in 1,4-dioxane (15 mL),To this was added cesium carbonate (4.0 g, 6.5 mmol) and palladium acetate (360 mg, 0.3 mmol).The reaction was stirred at 75 C for 3 hours.After the reaction, the reaction mixture was poured into ice water and extracted with ethyl acetate (100 mL×2).The combined organic layers were washed with brine, dried over anhydrous sodiumThe residue was subjected to column chromatography to give the product as a colorless oil.(734 mg, 53% yield); |
53% | With palladium diacetate; caesium carbonate; In 1,4-dioxane; at 75℃; for 3h; | Ethyl 2-bromo-4-chloroquinoline-3-carboxylate (1.1 g, 3.2 mmol) and (1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)boronic acid (0.69 g, 3.3 mmol) Dissolved in 1,4-dioxane (15 mL), cesium carbonate (4.0 g, 6.5 mmol) and palladium acetate (360 mg, 0.3 mmol) were added thereto, and the reaction mixture was stirred at 75 C for 3 hours. After completion, the reaction solution was poured into ice water and extracted with ethyl acetate (100 mL×2). The organic phase was combined, and the organic layer was washed with brine, dried over anhydrous sodium sulfateColorless oil (734 mg, 53%)rate); |
53% | With palladium diacetate; caesium carbonate; In 1,4-dioxane; for 3h;Heating; | Ethyl 2-bromo-4-chloroquinoline-3-carboxylate (1.0 g) and (1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)boronic acid (0.6 g) were dissolved in an appropriate amount of 1,4 In the dioxane, cesium carbonate (4.0 g) and palladium acetate (360 mg) were added thereto. The reaction solution was stirred at high temperature for 3 hours. After the reaction was completed, the reaction solution was poured into ice water and extracted with ethyl acetate (100 mL×2). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate The residue was purified by column chromatography (EtOAc: PET = 1: 30) to give the product as a colorless oil (53% yield). |
43% | With palladium diacetate; potassium carbonate; In 1,4-dioxane; at 50℃; for 3h; | Ethyl 2-bromo-4-chloroquinoline-3-carboxylate (3.2 mmol) and (1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)boronic acid (3.3 mmol) were dissolved in 1,4- Dioxane (15 mL),Potassium carbonate (6.5 mmol) and palladium(II) acetate (0.3 mmol) were added thereto, and the reaction mixture was stirred at 50 C for 3 hours.After the reaction was completed, the reaction solution was poured into ice water and extracted with ethyl acetate (100 mL×2).The organic phase is combined, the organic phase is washed with brine, dried over anhydrous sodium sulfate, filtered,Ethyl 2-(1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)-4-chloroquinoline-3-carboxylate (43% yield); |
43% | With palladium diacetate; potassium carbonate; In 1,4-dioxane; water; at 50℃; for 3h; | Ethyl 2-bromo-4-chloroquinoline-3-carboxylate (3.2 mmol) and (1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)boronic acid (3.3 mmol) were dissolved in 1,4- In dioxane (15 mL) and water (6 mL),Potassium carbonate (6.5 mmol) and palladium acetate (0.3 mmol) were added thereto, and the reaction mixture was stirred at 50 C for 3 hours.After the reaction is over, the reaction solution is poured into ice water.Extract with ethyl acetate (100 mL x 2).The organic phase was combined and the organic phase was washed with brine.Dry over anhydrous sodium sulfate, filter,Organic phase concentrate,The residue was subjected to column chromatography to ethyl 2-(1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)-4-chloroquinoline-3-carboxylate (43% yield); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water for 18h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 80℃; for 3h;Inert atmosphere; | General procedure: Under inert atmosphere, a mixture of benzaldehyde boronic acid or ester A2 (1.0 equiv.), (hetero)aromatic hade B2 (1.0 equiv.) and PdCI2(dppf).CH2CI2 (0.10 equiv.) in a mixture of dioxane (0.10 moLL1) and aqueous K3P04 (1.2 moLL1) was heated at 80C for 1 hour, After coong to room temperature, the reaction mixture was hydrolysed and extracted twice with EtOAc. The organic layers were combined, washed with brine, dried over MgSO4,concentrated and purified to afford the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In water; N,N-dimethyl-formamide at 80℃; for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; palladium diacetate; XPhos; In tetrahydrofuran; water; at 70℃;Inert atmosphere; | To a solution of 5.0 g (24 mmol) of <strong>[884494-81-9]3-bromo-5-fluoro-2-methoxypyridine</strong> in 100 mL of THF and 10 mL of H20 were added 5.1 g (24 mmol) of [1 -[(tert-butoxy)carbonyl]-1 H-pyrrol-2- yl]boronic acid, 0.27 g (1 .2 mmol) of Pd(OAc)2, 2.3 g (4.9 mmol) of XPhos and 15.4 g (72.8 mmol) of K3PO4 at rt. The mixture was stirred at 70 C for overnight under nitrogen atmosphere and cooled down to rt. It was diluted with 500 mL of water and extracted with 500 mL of ethyl acetate. The combined organic extracts were washed with brine and dried over anhydrous Na2S04. After filtration, the filtrate was concentrated to afford a residue, which was purified by chromatography on silica gel column eluting with 0 to 100 % gradient of ethyl acetate in petroleum ether to afford compound 7-1 . LC-MS: m/e = 293 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.4% | With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In water; N,N-dimethyl-formamide at 100 - 120℃; Inert atmosphere; | 1.1-1.9; 2.1-2.9 Example 2 (1) Put a suitable size electromagnetic stirrer into a 500 mL dried two-neck round bottom flask and weigh 2,7-dibromo-1,8-naphthyridine (1000 mg, 1.0 equiv.), 1-Boc- Pyrrole-2-boronic acid (1760 mg, 2.4 equiv.), bistriphenylphosphine palladium dichloride (487 mg, 0.2 equiv.) and potassium carbonate (2400 mg, 5.0 equiv.);(2) Vacuuming for 20 minutes, then purging with nitrogen for 10 minutes, repeated three times to achieve the desired conditions.(3) At the same time, another 500 mL one-necked flask was charged with N,N-dimethylformamide (200 mL) and water (100 mL), and the needle was inserted into the surface with a long needle and bubbled with nitrogen for 20 minutes;(4) Transfer N,N-dimethylformamide (200 mL) and water (100 mL) to a 500 mL two-neck round bottom flask using a double-ended needle;(5) Under nitrogen protection, the system is stirred and refluxed in an oil bath at 100~120 °C for 6~10 h;(6) After the reaction is completed, the reaction solution is removed under reduced pressure at a temperature of 60 to 80 ° C and a pressure of 10 to 40 mbar;(7) The crude product after removing the solvent is dissolved in dichloromethane, washed with water three times, and the dichloromethane phase is taken, and the solvent is removed at a temperature of 30 to 50 ° C and a pressure of 0.09 to 0.1 MPa;(8) The residue of the solvent is removed by column chromatography using 200 to 300 mesh silica gel as an adsorbent and dichloromethane as an eluent;(9) The dichloromethane is removed under reduced pressure at a temperature of 30 to 50 ° C and a pressure of 0.09 to 0.1 MPa to obtain a yellow solid.2,7-(1,1'-Dihydro)-1,8-naphthyridinium dipyrrole, 843 mg, yield 93.4%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; palladium diacetate; XPhos; In butan-1-ol; for 2h;Inert atmosphere; | General procedure: To a flame-dried 5 mL microwave vial flask equipped with a magnetic stir bar was added N-Boc-pyrrole-2-boronic acid (316 mg,1.5 mmol, 1.5 equiv), Pd(OAc)2 (4.5 mg, 0.02 mmol, 0.02 equiv), XPhos (19.0 mg, 0.04 mmol, 0.04 equiv), K3PO4 (424 g, 2.0 mmol, 2.0 equiv), and aryl bromide (1.0 mmol, 1.0 equiv). The flask was evacuated and backfilled with nitrogen three times, and then the gas line adapter was quickly replaced with a rubber septum and a balloon of nitrogen. To the flask was added degassed (by sonicationfor 30 min with N2 sparging), anhydrous n-butanol [2 mL (0.5M in ArBr)]. The heterogeneous reaction mixture was stirred vigorously for 2 h and then poured into ethyl acetate (~20 mL). This mixture was filtered through a pad of silica and concentrated under reduced pressure by rotary evaporation. This product was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; palladium diacetate; XPhos; In butan-1-ol; for 2h;Inert atmosphere; | General procedure: To a flame-dried 5 mL microwave vial flask equipped with a magnetic stir bar was added N-Boc-pyrrole-2-boronic acid (316 mg,1.5 mmol, 1.5 equiv), Pd(OAc)2 (4.5 mg, 0.02 mmol, 0.02 equiv), XPhos (19.0 mg, 0.04 mmol, 0.04 equiv), K3PO4 (424 g, 2.0 mmol, 2.0 equiv), and aryl bromide (1.0 mmol, 1.0 equiv). The flask was evacuated and backfilled with nitrogen three times, and then the gas line adapter was quickly replaced with a rubber septum and a balloon of nitrogen. To the flask was added degassed (by sonicationfor 30 min with N2 sparging), anhydrous n-butanol [2 mL (0.5M in ArBr)]. The heterogeneous reaction mixture was stirred vigorously for 2 h and then poured into ethyl acetate (~20 mL). This mixture was filtered through a pad of silica and concentrated under reduced pressure by rotary evaporation. This product was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran; water Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water; toluene for 10h; Heating; Inert atmosphere; |
Tags: 135884-31-0 synthesis path| 135884-31-0 SDS| 135884-31-0 COA| 135884-31-0 purity| 135884-31-0 application| 135884-31-0 NMR| 135884-31-0 COA| 135884-31-0 structure
[ 1072944-98-9 ]
tert-Butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-1-carboxylate
Similarity: 0.83
[ 913388-66-6 ]
(1-(tert-Butoxycarbonyl)-5-((tert-butoxycarbonyl)amino)-1H-indol-2-yl)boronic acid
Similarity: 0.77
[ 1217500-59-8 ]
(6-Bromo-1-(tert-butoxycarbonyl)-1H-indol-2-yl)boronic acid
Similarity: 0.69
[ 1072944-96-7 ]
tert-Butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate
Similarity: 0.67
[ 1072944-98-9 ]
tert-Butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-1-carboxylate
Similarity: 0.83
[ 913388-66-6 ]
(1-(tert-Butoxycarbonyl)-5-((tert-butoxycarbonyl)amino)-1H-indol-2-yl)boronic acid
Similarity: 0.77
[ 1217500-59-8 ]
(6-Bromo-1-(tert-butoxycarbonyl)-1H-indol-2-yl)boronic acid
Similarity: 0.69
[ 1072944-96-7 ]
tert-Butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate
Similarity: 0.67
[ 1072944-98-9 ]
tert-Butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-1-carboxylate
Similarity: 0.83
[ 209216-57-9 ]
tert-Butyl 3-formyl-1H-pyrrole-1-carboxylate
Similarity: 0.59
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :