* 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.
With N,N,N-trimethylbenzenemethanaminium dichloroiodate; calcium carbonate In methanol; dichloromethaneHeating / reflux
A solution of methyl 4-aminobenzoate (5.0 g; 0.033 mol.), benzyltrimethylammonium dichloroiodate (22.1 g; 0.056 mol.) and calcium carbonate (5.0 g; 0.050 mol.) in a mixture of dichloromethane (200 ml) and methanol (100 ml_) were stirred and heated under reflux overnight. The solution was cooled, washed with saturated sodium bisulphate, dried and evaporated to afford the desired product (9.6 g; quant.) which was used directly EPO <DP n="32"/>without further purification. 1 H NMR (400 MHz, DMSOd6) δ ppm 3.75 (s, 3 H) 6.09 (s, 2 H) 6.75 (d, J=8.59 Hz, 1 H) 7.66 (dd, J=8.59, 2.02 Hz, 1 H) 8.11 (d, J=2.02 Hz, 1 H).
100%
With N,N,N-trimethylbenzenemethanaminium dichloroiodate; calcium carbonate In methanol; dichloromethaneHeating / reflux
A solution of methyl 4-aminobenzoate (5.0 g; 0.033 mol.), benzyltrimethylammonium dichloroiodate (22.1 g; 0.056 mol.) and calcium carbonate (5.0 g; 0.050 mol.) in a mixture of dichloromethane(200 ml) and methanol (100 ml.) were stirred and heated under reflux overnight. The solution was cooled, washed with saturated sodium bisulphate, dried and evaporated to afford the desired product (9.6 g; quant.) which was used directly without further purification. 1 H NMR (400 MHz, DMSOd6) δ ppm 3.75 (s, 3 H) 6.09 (s, 2 H) 6.75 (d, J=8.59 Hz, 1 H)7.66 (dd, J=8.59, 2.02 Hz, 1 H) 8.1 1 (d, J=2.02 Hz, 1 H).
93%
With pyridine iodine monochloride In methanol for 2 h; Reflux; Inert atmosphere
To a stirred solution of methyl 4-aminobenzoate 18 (1.0 g, 6.62 mmol, 1.0 eq.) in methanol (60 mL) was added pyridinium iodochloride(1.60 g, 6.62 mmol, 1.0 eq.). The reaction mixture was refluxed for 2h under nitrogen atmosphere. After cooling to room temperature, the mixture was concentrated in vacuo. The reaction was diluted with ethyl acetate and washed with brine. The organic layer was dried over MgSO4 and was concentrated in vacuo. The crude was purified by chromatography on silica gel column (cyclohexane/EtOAc, gradient 100:0 to 70:30) and concentrated under reduced pressure to afford the compound 19, as a pale yellow solid (93percent yield); mp 90°C; 1H NMR (CDCl3, 500 MHz) δ 8.33 (d, 4J = 1.9 Hz, 1H), 7.81 (dd, 3J = 8.5 Hz, 4J = 2.0 Hz, 1H), 6.70 (d, 3J = 8.5 Hz, 1H), 4.53 (br s, 2H), 3.85 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 166.0 (CO), 150.9 (Cq), 141.2 (CH), 131.4 (CH), 121.4 (CH), 113.3 (Cq), 82.3 (Cq), 52.0 (CH3); IR (neat, cm-1) ν 3472, 3365, 2997, 2948, 2844, 1684, 1627, 1249, 764. Spectral and analytical data matched with literature.[2]
90%
With N-iodo-succinimide; [bis(trifluoromethanesulfonyl)imidate](triphenylphosphine)gold(I) In dichloromethane; toluene at 20℃; for 14 h;
General procedure: To a stirred solution of the substrate (1 mmol) in CH2Cl2 or (CH2Cl)2 (0.1 M) were added Ph3PAuNTf2 (0.025 mmol, 19 mg; complex Ph3PAuNTf2 toluene, 2:1) followed by N-iodosuccinimide (1.1 mmol, 248 mg). The resulting solution was stirred at r.t. or under reflux until complete conversion of the starting material. After removal of the solvent under reduced pressure, the crude material was purified by flash column chromatography using different gradients of hexanes and EtOAc to obtain the pure desired products.
73%
With Iodine monochloride In acetic acid at 20 - 30℃; for 1 h;
10,4 g (68,8 [MMOL) 4-AMINOBENZOESaeUREMETHYLESTER] wurden in 100 ml Essigsaeure geloest und mit 11,17 g (68,8 [MMOL)] [LODMONOCHLORID] in 100 ml Essigsaeure versetzt. Dabei stieg die Reaktionstemperatur [AUF 30°C] an. Nach einer Stunde bei Raumtemperatur wurde auf [10percent] ige Natriumhydrogencarbonat-Loesung gegossen, mit Dichlormethan extrahiert, die organische Phase getrocknet und eingeengt. Man erhielt 14 g (73 percent) des gewuenschten Produktes.
Reference：
[1] Patent: WO2007/38331, 2007, A2, . Location in patent: Page/Page column 30-31
[2] Patent: WO2007/103759, 2007, A2, . Location in patent: Page/Page column 48
[3] European Journal of Medicinal Chemistry, 2019, p. 234 - 248
[4] European Journal of Organic Chemistry, 2001, # 24, p. 4607 - 4613
[5] Synlett, 2014, vol. 25, # 3, p. 399 - 402
[6] Tetrahedron Letters, 2002, vol. 43, # 5, p. 787 - 790
[7] Advanced Synthesis and Catalysis, 2007, vol. 349, # 7, p. 1159 - 1172
[8] RSC Advances, 2014, vol. 4, # 36, p. 18930 - 18932
[9] Tetrahedron, 1990, vol. 46, # 13/14, p. 4587 - 4594
[10] Tetrahedron Letters, 1986, vol. 27, # 11, p. 1293 - 1296
[11] Journal of Organic Chemistry, 2003, vol. 68, # 5, p. 1843 - 1851
[12] Patent: WO2003/104188, 2003, A1, . Location in patent: Page 27, 28
[13] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 9, p. 2722 - 2725
[14] Tetrahedron Letters, 1997, vol. 38, # 14, p. 2439 - 2442
[15] Chemical Communications, 2017, vol. 53, # 24, p. 3481 - 3484
[16] Journal of Labelled Compounds and Radiopharmaceuticals, 1996, vol. 38, # 3, p. 227 - 237
[17] Organic Letters, 2005, vol. 7, # 10, p. 2043 - 2046
[18] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 21, p. 5646 - 5649
[19] Journal of Organic Chemistry, 2002, vol. 67, # 18, p. 6395 - 6405
[20] Patent: WO2008/73865, 2008, A2, . Location in patent: Page/Page column 62
[21] Patent: US2002/19527, 2002, A1,
[22] Patent: WO2007/138033, 2007, A1, . Location in patent: Page/Page column 33-34
3
[ 150-13-0 ]
[ 19718-49-1 ]
Reference：
[1] Acta Chemica Scandinavica (1947-1973), 1968, vol. 22, p. 538 - 548
[2] European Journal of Medicinal Chemistry, 2019, p. 234 - 248
4
[ 99512-09-1 ]
[ 19718-49-1 ]
Reference：
[1] Angewandte Chemie - International Edition, 2011, vol. 50, # 32, p. 7354 - 7358
With N,N,N-trimethylbenzenemethanaminium dichloroiodate; calcium carbonate; In methanol; dichloromethane;Heating / reflux;
A solution of methyl 4-aminobenzoate (5.0 g; 0.033 mol.), benzyltrimethylammonium dichloroiodate (22.1 g; 0.056 mol.) and calcium carbonate (5.0 g; 0.050 mol.) in a mixture of dichloromethane (200 ml) and methanol (100 ml_) were stirred and heated under reflux overnight. The solution was cooled, washed with saturated sodium bisulphate, dried and evaporated to afford the desired product (9.6 g; quant.) which was used directly EPO <DP n="32"/>without further purification. 1 H NMR (400 MHz, DMSOd6) delta ppm 3.75 (s, 3 H) 6.09 (s, 2 H) 6.75 (d, J=8.59 Hz, 1 H) 7.66 (dd, J=8.59, 2.02 Hz, 1 H) 8.11 (d, J=2.02 Hz, 1 H).
100%
With N,N,N-trimethylbenzenemethanaminium dichloroiodate; calcium carbonate; In methanol; dichloromethane;Heating / reflux;
A solution of methyl 4-aminobenzoate (5.0 g; 0.033 mol.), benzyltrimethylammonium dichloroiodate (22.1 g; 0.056 mol.) and calcium carbonate (5.0 g; 0.050 mol.) in a mixture of dichloromethane(200 ml) and methanol (100 ml.) were stirred and heated under reflux overnight. The solution was cooled, washed with saturated sodium bisulphate, dried and evaporated to afford the desired product (9.6 g; quant.) which was used directly without further purification. 1 H NMR (400 MHz, DMSOd6) delta ppm 3.75 (s, 3 H) 6.09 (s, 2 H) 6.75 (d, J=8.59 Hz, 1 H)7.66 (dd, J=8.59, 2.02 Hz, 1 H) 8.1 1 (d, J=2.02 Hz, 1 H).
93%
With pyridine iodine monochloride; In methanol; for 2h;Reflux; Inert atmosphere;
To a stirred solution of methyl 4-aminobenzoate 18 (1.0 g, 6.62 mmol, 1.0 eq.) in methanol (60 mL) was added pyridinium iodochloride (1.60 g, 6.62 mmol, 1.0 eq.). The reaction mixture was refluxed for 2h under nitrogen atmosphere. After cooling to room temperature, the mixture was concentrated in vacuo. The reaction was diluted with ethyl acetate and washed with brine. The organic layer was dried over MgSO4 and was concentrated in vacuo. The crude was purified by chromatography on silica gel column (cyclohexane/EtOAc, gradient 100:0 to 70:30) and concentrated under reduced pressure to afford the compound 19, as a pale yellow solid (93% yield); mp 90C; 1H NMR (CDCl3, 500 MHz) delta 8.33 (d, 4J = 1.9 Hz, 1H), 7.81 (dd, 3J = 8.5 Hz, 4J = 2.0 Hz, 1H), 6.70 (d, 3J = 8.5 Hz, 1H), 4.53 (br s, 2H), 3.85 (s, 3H); 13C NMR (CDCl3, 126 MHz) delta 166.0 (CO), 150.9 (Cq), 141.2 (CH), 131.4 (CH), 121.4 (CH), 113.3 (Cq), 82.3 (Cq), 52.0 (CH3); IR (neat, cm-1) nu 3472, 3365, 2997, 2948, 2844, 1684, 1627, 1249, 764. Spectral and analytical data matched with literature.[2]
90%
With N-iodo-succinimide; [bis(trifluoromethanesulfonyl)imidate](triphenylphosphine)gold(I); In dichloromethane; toluene; at 20℃; for 14h;
General procedure: To a stirred solution of the substrate (1 mmol) in CH2Cl2 or (CH2Cl)2 (0.1 M) were added Ph3PAuNTf2 (0.025 mmol, 19 mg; complex Ph3PAuNTf2 toluene, 2:1) followed by N-iodosuccinimide (1.1 mmol, 248 mg). The resulting solution was stirred at r.t. or under reflux until complete conversion of the starting material. After removal of the solvent under reduced pressure, the crude material was purified by flash column chromatography using different gradients of hexanes and EtOAc to obtain the pure desired products.
73%
With Iodine monochloride; In acetic acid; at 20 - 30℃; for 1h;
10,4 g (68,8 [MMOL) 4-AMINOBENZOESaeUREMETHYLESTER] wurden in 100 ml Essigsaeure geloest und mit 11,17 g (68,8 [MMOL)] [LODMONOCHLORID] in 100 ml Essigsaeure versetzt. Dabei stieg die Reaktionstemperatur [AUF 30C] an. Nach einer Stunde bei Raumtemperatur wurde auf [10%] ige Natriumhydrogencarbonat-Loesung gegossen, mit Dichlormethan extrahiert, die organische Phase getrocknet und eingeengt. Man erhielt 14 g (73 %) des gewuenschten Produktes.
46%
With N-iodo-succinimide; In tetrahydrofuran; at 20℃;
1002911 A flask was charged with methyl 4-aminobenzoate (9.00 g, 59.5 mmol, 1.00 equiv), THF (100 mL) and 1-iodo-5-pyrrolidinedione (16.2 g, 72.0 mmol, 1.20 equiv). The resulting solution was stirred overnight at room temperature and concentrated under reduced pressure. The residue was diluted with water (50 mL) and extracted with DCM (3 x 50 mL), the organic layers were combined, washed with water (3 x 50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column to provide 7.60 g (46% yield) of methyl 4-amino-3-iodobenzoate as a yellow solid. LCMS (ESI, m/z):278 [M+H].
46%
With N-iodo-succinimide; at 20℃;
A flask was charged with methyl 4-aminobenzoate (9.00 g, 59.5 mmol, 1.00 equiv), THF (100 mL) and l-iodo-5-pyrrolidinedione (16.2 g, 72.0 mmol, 1.20 equiv). The resulting solution was stirred overnight at room temperature and concentrated under reduced pressure. The residue was diluted with water (50 mL) and extracted with DCM (3 x 50 mL), the organic layers were combined, washed with water (3 x 50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column to provide 7.60 g (46% yield) of methyl 4-amino-3-iodobenzoate as a yellow solid. LCMS (ESI, m/z): 278 [M+H]+.
With N,N,N-trimethylbenzenemethanaminium dichloroiodate; In dichloromethane; acetic acid; at 20 - 55℃; for 1.5h;
To a solution of 4-amino-benzoic acid methyl ester (Ig) in 10 mL of acetic acid and 10 mL OfCH2Cl2 was added benzyltrimethylammonium dichloroiodate (2.763g) at ambient temperature. The reaction mixture was heated at 55 0C for 1.5h. The reaction mixture was concentrated to give the crude 4-amino-3-iodo-benzoic acid methyl ester: MS (m/z) 278.0 (M+l).
EXAMPLE 93D methyl 4-amino-3-iodobenzoate The desired product was prepared by substituting methyl-4-aminobenzoate for ethyl-4-aminobenzoate in Example 93A.
With N-iodo-succinimide; In N,N-dimethyl-formamide; at 20℃;
Description 13: Methyl 4-amino-3-iodobenzoate; A suspension of methyl 4-aminobenzoate (4.53g, 30mmol) and N-iodosuccinimide (6.75g, 30mmol) in dimethylformamide (5OmL) was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with water, 5% sodium thiosulphate solution and water, dried (magnesium sulphate) and evaporated. The residue <n="35"/>was purified by flash chromatography [silica gel, ethyl acetate/hexane (0-25%)] to yield the title compound (8.2g) as a yellow solid. LC/MS (ES+ve): [M+H]+ at m/z 278 (C8H8INO2 requires [M+H]+ at m/z 278).
With water; lithium hydroxide; In 1,4-dioxane; at 20℃; for 6h;
A solution of 3.00 g (10.8 mmol) of methyl 4-amino-3-iodobenzoate and 1.30 g (54.1 mmol) of lithium hydroxide in 150 ml of a dioxane/water mixture (1:1) was stirred at room temperature for 6 h. The dioxane was distilled off in vacuo, and the remaining aqueous phase was adjusted to pH 5 with 1 M hydrochloric acid. The precipitate was filtered off with suction and washed with water. 2.80 g (98%) of the title compound were obtained as a solid. HPLC (Kromasil RP-18, 60*2.1 mm, eluent=A: H2O+5 mL HClO4/L; B: acetonitrile; gradient=0-4.5 min 98% A-90% B; 4.5-6.5 min 90% B; 0.75 mL/min; temp.: 30 C., UV detection at 21 nm): Rt=3.51 min 1H-NMR (300 MHz in D6-DMSO) delta=5.98 (s, 2H), 6.74 (d, 1H), 7.63 (m, 1H), 8.10 (s, 1H), 12.33 (s, broad, 1H) MS (ESI+): m/z=281 [M+NH4]+
94%
With sodium hydroxide; In ethanol;Inert atmosphere;
General procedure: To a stirred solution of methyl ester derivatives (1.0 eq.) in EtOH (10 mL/mmol) was added a 1N NaOH solution (10.0 eq.) under nitrogen atmosphere at room temperature. The resulting mixture was stirred overnight at room temperature, and then concentrated in vacuo to remove EtOH. The residue was diluted with water. The aqueous layer was acidified by addition of hydrochloric acid until acidic pH, and extracted several times with ethyl acetate. The combined organic extract was washed with brine, dried over MgSO4 and concentrated under reduced pressure to give the title compounds 7a-c.
89%
With sodium hydroxide; In methanol; water; at 20℃; for 16h;
6,0 g (21,7 [MMOL)] [4-AMINO-3-IODOBENZOESaeUREMETHYLESTER] wurden mit 1, [73 G] (43,3 [MMOL)] Natriumhydroxid in 100 [ML METHANOL] und 100 ml [H20] versetzt und 16 Stunden bei Raumtemperatur geruehrt. Es wurde mit 2 N Salzsaeure auf pH 9 gestellt und mit Essigsaeureethylester extrahiert. Die organische Phase wurde getrocknet, und eingeengt. Man erhielt 5,1 g (89 [%)] des gewuenschten Produktes.
STEP D: 4-Amino-N-(3,4-dimethoxyphenyl)-3-iodobenzamide A 500 mL round bottom flask was charged with methyl 4-amino-3-iodobenzoate (10.0 g, 36.1 mmol), methanol (270 mL), water (30 mL), and lithium hydroxide (1.82 g, 43.3 mmol). The vessel was flushed with nitrogen, fit with a reflux condenser, and the mixture heated to a gentle reflux for 20 h. The resulting mixture was then cooled to room temperature, acidify with 2N hydrochloric acid, then concentrated in vacuo. A 500 mL round bottom flask was charged with the resulting solid (9.5 g, 36.7 mmol) and dichloromethane (180 mL) was added. Bis(2-oxo-3-oxazolidinyl)phosphinic chloride (10.0 g, 39.5 mmol) and triethylamine (11.1 mL, 79.2 mmol) were added. 3,4-Dimethoxyaniline (11.1 g, 72.1 mmol) was then added and the resulting mixture was stirred at room temperature for 24 h. The resulting mixture was then diluted with ethyl acetate and washed with 1N NaOH. The organic layer was dried with MgSO4, filter, then concentrate in vacuo to yield 4-amino-N-(3,4-dimethoxyphenyl)-3-iodobenzamide. 1H NMR (300 MHz, CDCl3) delta 8.23 (s, 1 H), 7.73 (d, J=8.5 Hz, 1H), 7.42 (s, 1H), 7.30 (d, J=8.6 Hz, 1H), 6.90 (d, J=8.8 Hz, 1H), 6.77 (d, J=8.5 Hz, 1H), 3.74 (s, 3H), and 3.72 (s, 3H).
A solution (0.26 M) of the substrate in dry THF was treated dropwise at 0 C with TFAA (2 eq). The mixture was stirred for 10 min, then adjusted to pH 8 by addition of saturated aqueous NaHC03. The mixture was extracted with AcOEt and the organic phase was washed with brine then dried. Removal of the solvent gave the title compound (100 %) as a solid. 'H NMR (300 MHz, DMSO-d6) 8 3.89 (s, 3H), 7.57 (d, J 8. 2 Hz, 1H), 8.03 (dd, J 1.9, 8.2 Hz, 1H), 8.44 (d, J 1.9 Hz, 1H)
96%
With triethylamine; In dichloromethane; at 0℃; for 1.5h;
A solution of methyl 4-amino-3-iodobenzoate (100 mg,0.36 mmol) and triethylamine (101 mu, 0.72 mmol) in DCM (3 ml) was added dropwise to a cooled (0 C) solution of trifluoroacetic acid anhydride (127 mu, 0.90 mmol) in DCM (1 ml). The cooling bath was removed and the mixture was stirred for 1.5 h. The crude product was poured into cold water and DCM was added. The phases were separated; solvents were removed in vacuo and the crude product taken to the next step without further purification. Yield: 129 mg (96%); white solid. MS (ESI+) m z 374 [M+H]+. HPLC purity: 96%. 1H NMR (600 MHz, CDC13) delta ppm 8.51 (d, J=1.83 Hz, 1 H) 8.47 (br. s., 1 H) 8.36 (d, J=8.54 Hz, 1 H) 8.08 (dd, J=8.85, 1.83 Hz, 1 H) 3.93 (s, 3 H).
91%
With triethylamine; In dichloromethane; at 0 - 20℃; for 3h;
A solution of methyl 4-amino-3-iodobenzoate (1.0 g, 3.61 mmol) and triethylamine (1.003 mL, 7.22 mmol) in dichloromethane (20 mL) was added dropwise to a cooled (0 C.) solution of trifluoroacetic anhydride (1.275 mL, 9.02 mmol) in dichloromethane (5 mL). The cooling was removed, the mixture was stirred at room temperature for 3 hours, poured into ice-water and extracted with dichloromethane. The organic phase was dried over sodium sulfate and the solvent was evaporated. Purification by column chromatography, using heptane/ethyl acetate (4:1) as the eluent, gave 1.23 g (91% yield) of the title compound.1H NMR (500 MHz, CD3OD) delta ppm 8.54 (d, 1H) 8.07 (dd, 1H) 7.57 (d, 1H) 3.93 (s, 3H); MS (ESI) m/z 372 [M-1]-.
91%
With triethylamine; In dichloromethane; at 20℃; for 3h;
A solution of methyl 4-amino-3-iodobenzoate (1.0 g, 3.61 mmol) and triethylamine (1.003 mL, 7.22 mmol) in dichloromethane (20 mL) was added dropwise to a cooled (0 0C) solution of trifiuoroacetic anhydride (1.275 mL, 9.02 mmol) in dichloromethane (5 mL). The cooling was removed, the mixture was stirred at room temperature for 3 hours, poured into ice-water and extracted with dichloromethane. The organic phase was dried over sodium sulfate and the solvent was evaporated. Purification by column chromatography, using heptane/ethyl acetate (4:1) as the eluent, gave 1.23 g (91% yield) of the title compound. <n="146"/>1H NMR (500 MHz, CD3OD) delta ppm 8.54 (d, 1 H) 8.07 (dd, 1 H) 7.57 (d, 1 H) 3.93 (s, 3 H); MS (ESI) m/z 372 [M-I]".
79%
With triethylamine; In dichloromethane; at 20℃;
j00292J A round-bottom flask was charged with methyl 4-amino-3-iodobenzoate (7.50 g, 27.1 mmol, 1.00 equiv), DCM (50 mL), triethylamine (7.20 g, 71.3 mmol, 2.63 equiv) and trifluoroacetic anhydride (8.90 g, 42.4 mmol, 1.57 equiv). The resulting solution was stirred overnight at room temperature and washed with water (3 x 50 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure, as described in Example 1, Step 1. The residue was chromatographed on a silica gel column to provide 8.00 g (79% yield) of methyl 3 -iodo-4-(2,2,2-trifluoroacetamido)benzoate as a yell ow solid.
79%
With triethylamine; In dichloromethane; at 20℃;
A flask was charged with methyl 4-amino-3-iodobenzoate (7.50 g, 27.1 mmol, 1.00 equiv), DCM (50 mL), triethylamine (7.20 g, 71.3 mmol, 2.63 equiv) and trifluoroacetic anhydride (8.90 g, 42.4 mmol, 1.57 equiv), as described in Example 1, Step 1. The residue was chromatographed on a silica gel column to provide 8.00 g (79% yield) of methyl 3-iodo-4- (2,2,2-trifluoroacetamido)benzoate as a yellow solid.
With caesium carbonate; lithium chloride;palladium diacetate; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; at 100℃; for 3h;
Intermediate 1; Methyl 2-(trimethylsilyl)-3-f2-r(trimethylsilyl)oxy1ethyl)-1H-indole-5-carboxylate; Methyl 4-amino-3-iodobenzoate (27.7 g, 0.1 mol), LiCI (4.24 g, 0.1 mol), Cs2CO3 (81.5 g, 0.25 mol), tri(o-tolyl)phosphine (1.52 g, 5 mmol) was added to DMF (500 ml). The mixture was degassed with nitrogen and 4-trimethylsilyl-3-butyn-1-ol (26.67 ml, 0.16 mol) and palladium (II) acetate (1.12 g, 5 mmol) was added, The mixture was degassed with nitrogen and stirred at 100 0C for 3 hours. The reaction mixture was filtered on celite (5 cm) and evaporated. The crude extract was diluted with ethyl acetate, the organic phase was washed with brine and dried over Na2SO4, filtered and concentrated. The residue was purified on SiO2 eluting with dichloromethane/ethyl acetate 95/5 to give a first fraction of the title compound (2.1 g) and a second fraction after evaporation and addition of heptane, precipitation and filtration : (Intermediate 1) (19.3 g, 66 %). LC/MS : m/z 292 (M+H)+, Rt: 2.96
(i) 1H-Indole-2,5-dicarboxylic acid 5-methyl ester A solution of 25 g <strong>[19718-49-1]4-Amino-3-iodo-benzoic acid methyl ester</strong>, 19 ml 2-Oxo-propionic acid, 30.4 g 1,4-Diaza-bicyclo[2.2.2]octane and 1 g Pd(OAc)2 was heated under argon to 100 C. After 5 h the reaction mixture was concentrated under reduced pressure and the residue was partitioned between 300 ml ethyl acetate and 200 ml 1 M hydrochloric acid. The organic layer was dried over MgSO4 and the solvent removed under reduced pressure to yield a yellow solid (6.4 g). From the aqueous layer additional product slowly precipitated as a white solid (7.9 g) which was collected by filtration. Both fractions were combined, dried in vacuo and used in the next reaction without further purification. Yield: 14.3 g MS (ES+): m/e=220.
With 1,4-diaza-bicyclo[2.2.2]octane;palladium diacetate; In DMF (N,N-dimethyl-formamide); at 100℃; for 5h;
A solution of 25 g <strong>[19718-49-1]4-Amino-3-iodo-benzoic acid methyl ester</strong>, 19 ml 2-Oxo-propionic acid, 30.4 g 1,4-Diaza-bicyclo[2.2.2]octane and 1 g Pd(OAc)2 in 200 ml DMF was heated under argon to 100C. After 5 h the reaction mixture was concentrated under reduced pressure and the residue was partitioned between 300 ml ethyl acetate and 200 ml 1 M hydrochloric acid. The organic layer was dried over MgSO4 and the solvent removed under reduced pressure to yield a yellow solid (6.4 g). From the aqueous layer additional product slowly precipitated as a white solid (7.9 g) which was collected by filtration. Both fractions were combined, dried in vacuo and used in the next reaction without further purification. Yield: 14.3 g MS (ES+): m/e =220.
With 1,4-diaza-bicyclo[2.2.2]octane;palladium diacetate; In N,N-dimethyl-formamide; at 100℃; for 5h;
(a) 1H-Indole-2,5-dicarboxylic acid 5-methyl ester A solution of 25 g 4-Amino-3-Iodo-benzoic acid methyl ester, 19 ml 2-Oxo-propionic acid, 30.4 g 1,4-Diaza-bicyclo[2.2.2]octane and 1 g Pd(OAc)2 in 200 ml DMF was heated under argon to 100 C. After 5 h the reaction mixture was concentrated under reduced pressure and the residue was partitioned between 300 ml ethyl acetate and 200 ml 1 M hydrochloric acid. The organic layer was dried over MgSO4 and the solvent removed under reduced pressure to yield a yellow solid (6.4 g). From the aqueous layer additional product slowly precipitated as a white solid (7.9 g) which was collected by filtration. Both fractions were combined, dried in vacuo and used in the next reaction without further purification. Yield: 14.3 g. MS (ES+): m/e=220.
With dmap; triethylamine; In dichloromethane; at 40℃;
A mixture of methyl 4-amino-3-iodobenzoate (5. OG, 18.0 mmol), di-tert-butyl dicarbonate (4.7g, 21.7 mmol), triethylamine (7.6 mL, 54.2 mmol), 4- (dimethylamino) pyridine (22mg, 0.18 mmol), and dichloromethane (150 mL) was heated overnight at 40 C, cooled to room temperature, concentrated under vacuum, diluted with ethyl acetate, washed with water and brine, dried (MGS04), filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel to give the 3.4g (50%) of the desired product. MS (ESI) m/e 395 (M+NH4) + ; IH NMR (300 MHz, DMSO-D6) 8 8.51 (s, 1H), 8.33 (d, J=2.0 Hz, 1H), 7.92 (dd, J=2.0, 8.5 Hz, 1H), 7.67 (d, J=8.5 Hz, 1H), 3.84 (s, 3H), 1.48 (s, 9H).
5 Synthesis of 4-Amino-3-(4,4,5,5-tetramethyl-(1,3.2)dioxaborolan-2-yl)-benzoic acid methyl ester 2
Example 5 Synthesis of 4-Amino-3-(4,4,5,5-tetramethyl-(1,3.2)dioxaborolan-2-yl)-benzoic acid methyl ester 2 Under argon atmosphere: To a mixture of methyl 4-amino-3-iodo-benzoate 1 (2.27 g, 8.19 mmol) in 1,4-dioxane (20 ml), triethylamine (4.6 ml, 33 mmol) and PdCl2(dppf) (0.30 g, 0.4 mmol), pinacolborane (3.6 ml, 25 mmol) was added dropwise at rt. Full conversion was reached after 8 h at 80° C. as indicated by TLC. The reaction was slowly quenched with sat. NH4Cl (aq) and the aqueous phase was extracted with diethyl ether. After drying over MgSO4, the solution was filtered over a patch of silica. Subsequently the silica was washed with methylene chloride. Concentration of the solution in vacuo gave 0.49 g of a mixture of the product and methyl-4-aminobenzoate. 1H NMR (400 MHz, CDCl3): 6=8.310 (d, J=2 Hz, 1H), 6=7.888 (d, J=2.4 Hz, 1H), 6=6.551 (d, J=8.8 Hz, 1H), 6=3.844 (s, 3H), 6=5.184 (bs, 2H), 6=1.346 (s, 12H).
Preparation Example F-1. 3-Acetyl-4-amino-benzoic acid methyl ester To a solution of 4-amino-3-iodo-benzoic acid methyl ester (11.30g, 40.77mmol) in toluene (300mL) were added tributyl(1-ethoxyvinyl)tin (16.5mL, 48.9mmol) and tetrakis(triphenylphosphine)palladium(0) (9422mg, 8.154mmol) under nitrogen atmosphere, and the solution was stirred at 105C for 7 hours. After cooling to room temperature, water was added, the mixture was extracted with ethyl acetate-tetrahydrofuran, the organic layer was washed with water, and then, evaporated. The residue was dissolved in 280mL of tetrahydrofuran, 2N hydrochloric acid (80mL) was added thereto, followed by stirring for 3 hours at room temperature. The reaction mixture was cooled on an ice bath, an aqueous solution of 2N sodium hydroxide (80mL) was added, an aqueous solution of saturated sodium bicarbonate was further added, and the solution was extracted with ethyl acetate. An aqueous solution of 10% potassium fluoride was added to the organic layer, and the solution was stirred for 3 hours at room temperature. The organic layer was separated, washed with brine, then evaporated, the residue was purified by silica gel column chromatography (hexane-ethyl acetate), and title compound (6.42g, 33.2mmol, 81.4%) was obtained. 1H-NMR Spectrum (CDCl3) delta (ppm): 2.64 (3H, s), 3.89 (3H, s), 6.63 (1H, d, J=8.8Hz), 7.91 (1 H, dd, J=2.0, 8.8Hz), 8.47 (1 H, d, J=2.0Hz).
With sodium carbonate; lithium chloride;palladium diacetate; In N,N-dimethyl-formamide; at 100℃; for 16h;
To a solution of Intermediate 25 (4.4 g, 14.8 mmol) dissolved in DMF (25 mL) was added methyl 4-amino-3-iodobenzoate (4.1 g, 14.8 mmol), LiCl (0.627 g, 14.8 mmol), Na2CO3 (3.1 g, 29.6 mmol) and Pd(OAc)2 (0.130 g, 0.59 mmol) and the reaction mixture was degassed under vacuum and then purged with nitrogen. The reaction mixture was then heated at 1000C for 16 h. The crude reaction mixture was cooled to r.t. and the solvent removed in vacuo to give a brown oil. The crude residue was partitioned between DCM (200 mL) and water (100 mL) and the organic fraction was dried using an Isolute phase separator cartridge and concentrated in vacuo to give a dark brown oil. Purification by column chromatography (SiO2, 10-25% EtOAc/hexanes) gave the title compound (3.90 g, 59%) as a yellow sticky solid. LCMS (ES+) 392.0 ((M-'Bu)+eta)+, RT 3.58 minutes {Method 2).
19%
With sodium carbonate; lithium chloride;palladium diacetate; In N,N-dimethyl-formamide; at 110℃; for 0.833333h;
INTERMEDIATE 42 <n="114"/>Methyl 3-[(3^-4-(tert-butoxycarbonvnmorpholin-3-yl1methvU-2-ftrimethylsilyl')-l//- intlupsilonle-5-earbupsilonxyldleTo a stirred solution of Intermediate 41 (31.9 g, 107.4 mmol) in DMF (160 mL) was added methyl 4-amino-3-iodobenzoate (29.8 g, 107.4 mmol), lithium chloride (4.5 g, 107.4 mmol) and sodium carbonate (22.8 g, 214.8 mmol). The resulting suspension was degassed before addition of palladium acetate (0.96 g, 4.3 mmol). The reaction mixture was heated to 11O0C for 50 minutes. It was cooled to r.t, filtered through celite, and concentrated in vacuo. The resulting brown oil was partitioned between isopropyl acetate and water (150 mL each). The aqueous fraction was extracted with isopropyl acetate (2 x 15OmL). The combined organic fractions were dried (MgSO4), treated with decolourising charcoal (5% by weight of crude material) for 30 minutes at room temperature, concentrated in vacuo and then purified by column chromatography (SiO2, DCM) to give the title compound (9g, 19%) as a pale cream solid. LCMS (ES+) 469.1 (M+ Na), RT 4.62 minutes {Method ).
19%
With sodium carbonate; lithium chloride;palladium diacetate; In N,N-dimethyl-formamide; at 110℃; for 0.833333h;
To a stirred solution of Intermediate 14 (31.9 g, 107 mmol) in DMF (160 ml) was added methyl 4-amino-3-iodobenzoate (29.8 g 107 mmol), LiCl (4.5 g 107 mmol) and Na2CO3 (22.8 g 215 mmol). The resulting suspension was degassed, Pd(OAc)2 (0.96 g, 4.3 mmol) added, and degassing repeated. The reaction mixture was heated to HO0C for 50 minutes. The reaction mixture was then cooled to room temperature, filtered through celite and concentrated in vacuo. The resulting brown oil was separated between isopropyl acetate and water. The aqueous layer was back-extracted with isopropyl acetate (2 x 150 mL). The combined organic layers were dried (MgSO4), treated with decolourising charcoal (5% by weight of crude material) for 30 minutes at room temperature, and purified by column chromatography (SiO2, DCM) to give the title compound (9.0 g, 19%) as a pale cream solid. deltaeta (CDCl3) 8.50 (IH, br s), 8.05 (IH, s), 7.88 (IH, d), 7.32 (IH, d), 4.32 (IH, m), 3.99 (IH, t), 3.91 (3H, s), 3.65 (IH, d), 3.50-3.28 (3H, m), 3.05 (IH, dd), 1.48 (9H, s), 0.40 (9H, s). LCMS (ES+) 469.1 (M+Na).
With caesium carbonate; lithium chloride;palladium diacetate; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; at 100℃; for 3h;
Intermediate 4; Methyl 3-r2-alpha2-r(1.1-dimethylethyl)oxy1-2-oxoethyl)oxy)ethv?-2-(trimethylsilyl)-1H- indole-5-carboxylate FOPI/U1435/60/1; <n="29"/>Pd(OAc)2 (106 mg, 0.47 mmol) was added to a solution of methyl 4-amino-3-iodobenzoate (2.58 g, 9.3 mmol), 1 ,1-dimethylethyl [4-(trimethylsilyl)-3-butyn-1-yl]oxy}acetate (Intermediate 3) (3.8 g, 14.8 mmol), LiCI (394 mg, 9.3 mmol), Cs2CO3 (7.58 g, 23.25 mmol) and tri-o-tolylphosphine (143 mg, 0.47 mmol) in anhydrous DMF. The reaction mixture was stirred at 100 0C for 3 hours. The reaction mixture was filtered and rinse with dichloromethane. The filtrate was washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified on SiO2 eluting with dichloromethane to give the title compound (1.65 g, 44%). LC/MS : m/z 406 (M+H)+, Rt: 3.96.
4-Amino-3-iodo-iV,./V-dimethylbenzamide < To a stirred solution of dimethylamine (9.0 mL, 135 mmol) in THF at O0C was added trimethylaluminium (50 mL, 2.0M solution in toluene, 100 mmol). The resulting solution was stirred at 00C for 10 minutes before addition of a solution of methyl 4- amino-3-iodobenzoate (19 g, 70 mmol) in THF (50 mL). The solution was heated to reflux for 1.5 h then allowed to cool to r.t before being poured onto ice (100 g). The resulting suspension was treated with aqueous 2M NaOH solution (100 mL) and partitioned with diisopropyl ether (2 x 100 mL). The combined organics were passed through a phase separator and concentrated to give the title compound (20 g, 96%) as a pale yellow oil which was used without further purification. 5H (CDCl3) 7.79 (IH, d, J <n="79"/>1.5 Hz), 7.29-7.26 (IH, m), 6.72 (IH, d, J8.2 Hz), 4.31 (2H, br. s), 3.07 (6H, s). LCMS (ES+) 261 (M+H)+.
With N(CH2CH3)3 In 1,4-dioxane (Ar); addn. of triethylamine, palladium compd. and borane deriv. to dioxane soln. of aniline deriv., heating at 100°C for 5 h; cooling to room temp., filtration through celite with eluting by ethyl acetate, evapn., chromy. (silica gel, hexane/ethyl acetate (9/1 to 5/5)),NMR and MS;
58%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine In 1,4-dioxane at 100℃; for 5h; Inert atmosphere;
With tetrakis(triphenylphosphine) palladium(0); barium hydroxide octahydrate; triethylamine; In 1,4-dioxane; water; at 90℃; for 8h;Inert atmosphere;
General procedure: To a solution of vinyl bromide a-c (6.7 mmol) in dioxane (30 mL) at 25 C under argon were successively added Et3N (3.70 mL, 26.9 mmol), Pd (PPh3)4 (779 mg, 0.670 mmol), and pinacolborane (2.90 mL, 20.2 mmol) dropwise. The solution was heated to 80 C for 1 h. After cooling, water (5 mL) was added dropwise followed by methyl 4-amino-3-iodobenzoate (1.5 g, 5.4 mmol) dissolved in dioxane (15 mL) and Ba(OH)2·8H2O (6.40 g, 20.2 mmol). The solution was heated to 90 C for 8 h. After cooling, the mixture was filtered through Celite, brine was added (40 mL), and the solution was extracted with ethyl acetate (3 × 50 mL). After drying over magnesium sulfate and evaporation of the solvents under vacuum, the residue was purified by flash chromatography to obtain the benzoates.
With tetrakis(triphenylphosphine) palladium(0); barium hydroxide octahydrate; triethylamine; In 1,4-dioxane; water; at 90℃; for 8h;Inert atmosphere;
General procedure: To a solution of vinyl bromide a-c (6.7 mmol) in dioxane (30 mL) at 25 C under argon were successively added Et3N (3.70 mL, 26.9 mmol), Pd (PPh3)4 (779 mg, 0.670 mmol), and pinacolborane (2.90 mL, 20.2 mmol) dropwise. The solution was heated to 80 C for 1 h. After cooling, water (5 mL) was added dropwise followed by methyl 4-amino-3-iodobenzoate (1.5 g, 5.4 mmol) dissolved in dioxane (15 mL) and Ba(OH)2·8H2O (6.40 g, 20.2 mmol). The solution was heated to 90 C for 8 h. After cooling, the mixture was filtered through Celite, brine was added (40 mL), and the solution was extracted with ethyl acetate (3 × 50 mL). After drying over magnesium sulfate and evaporation of the solvents under vacuum, the residue was purified by flash chromatography to obtain the benzoates.
With pyridine; at 0 - 20℃; for 16.5h;Inert atmosphere;
To a stirred solution of <strong>[19718-49-1]4-amino-3-iodo-benzoic acid methyl ester</strong> (11.1 g, 40.0 mmol) in pyridine (80 mL) was added acetyl chloride (3.30 g, 42.0 mmol) at 0 C. under nitrogen. Stirring continued at 0 C. for 30 minutes. The ice-bath was removed, and stirring continued at room temperature for 16 hours. Pyridine was evaporated under reduced pressure. The residue was taken in ethyl acetate (300 mL). The organic phase was washed with 2 N aqueous HCl (200 mL), water (200 mL), brine (200 mL), and then dried over anhydrous Na2SO4. Removal of solvent gave 4-acetylamino-3-iodo-benzoic acid methyl ester as a white solid. Yield: 12.71 g (99%)
99%
With pyridine; at 0 - 20℃; for 16.5h;Inert atmosphere;
Example 55 Preparation of 2-(2-(2-Hydroxyethyl)-1H-indol-5-yl)-5,7-dimethoxyquinazolin-4(3H)-one To a stirred solution of <strong>[19718-49-1]4-amino-3-iodo-benzoic acid methyl ester</strong> (11.1 g, 40.0 mmol) in pyridine (80 mL) was added acetyl chloride (3.30 g, 42.0 mmol) at 0 C. under nitrogen. Stirring continued at 0 C. for 30 minutes. The ice-bath was removed, and stirring continued at room temperature for 16 hours. Pyridine was evaporated under reduced pressure. The residue was taken in ethyl acetate (300 mL). The organic phase was washed with 2 N aqueous HCl (200 mL), water (200 mL), brine (200 mL), and then dried over anhydrous Na2SO4. Removal of solvent gave 4-acetylamino-3-iodo-benzoic acid methyl ester as a white solid. Yield: 12.71 g (99%).
> 99%
With triethylamine; In dichloromethane; at 0 - 20℃;
General procedure: A solution of 2-iodoaniline (333.6 mg, 1.52 mmol, 1.0 equiv) in DCM (5.0 mL) was added with Et3N (0.23 mL, 166.9 mg, 1.65 mmol, 1.1 equiv). The reaction solution was cooled at 0 C and acetyl chloride (0.28 mL, 308 mg, 3.92 mmol, 2.6 equiv) was added into the cooled solution. The resulting mixture was warmed to stir at room temperature overnight. Upon completion, thereaction was added with water and the separated aqueous phase was extracted with EtOAc (3xtimes). The combined organic phases were washed with sat. aq. NaCl, dried over anh. Na2SO4 and concentrated under reduced pressure. The crude material was purified by SiO2 column chromatography eluting with 30% EtOAc-hexane to yield 387.9 mg (98%) of the corresponding N-(2-iodophenyl)acetamide as a white solid.
methyl 4-[(5-tert-butyl-2-hydroxybenzene)amido]-3-iodobenzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
33%
In 5,5-dimethyl-1,3-cyclohexadiene Cooling with ice;
40 Methyl 4-[(5-tert-butyl-2-hydroxybenzene)amido]-3-iodobenzoate
Methyl 4-[(5-tert-butyl-2-hydroxybenzene)amido]-3-iodobenzoate was prepared in a similar manner as described in WO/2010/101648A1 from 5-tert-butyl-2-hydroxybenzoic acid [prepared as described in WO20051 10996A1] and methyl 4-amino-3-iodobenzoate [ACROS Chemicals] except the xylenes solution was chilled in an ice bath and vigorously stirred before the product was filtered to give a 33% yield of methyl 4-[(5-tert-butyl-2- hydroxybenzene)amido]-3-iodobenzoate as an off-white solid, MS: m/z 452 (MH") and m/z 454 (MH+). 1H NMR (500 MHz, DMSO-d6): δ 1.280 (s, 9H), 3.850 (s, 3H), 7.006 (d, 1H), 7.517 (dd, 1H), 7.989 (dd, 1H), 8.028 (d, 1H), 8.408 (d, 1H), 8.419 (d, 1H), 10.764 (s, 1H), 11.775 (s, 1H).
2-(5-fluoro-3-pyridinyl)-6-benzothiazolecarboxylic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
0.66 g
With sulfur; 1,10-Phenanthroline; copper(II) choride dihydrate; water; potassium carbonate; for 16h;Reflux;
Methyl 4-amino-3-iodobenzoate (1.93 g, 6.96 mmol) was combined with K2C03 (1.92g), 8 (668 mg), CuC12-2H20 (119 mg), 1,10-phenanthroline (125 mg) and <strong>[39891-04-8]5-fluoro-3-pyridinecarboxaldehyde</strong> (957 mg) in H20 (30 mL), and the reaction mixture was heated at reflux 16 hours. The cooled reaction mixture was filtered, and the filtrate was treated with NH4C1 (1.49 g). The reaction mixture was stirred at ambient temperature for 10 minutes, filtered, and the solid was dried in vacuo to yield a gray solid. The solid was suspended in dioxane, the suspension was heated to reflux, cooled, and filtered to isolate a solid. Thesolid was rinsed with ethyl ether to give the title compound (0.66 g). ?H NMR (DMSO-d6) oe: 9.15 (s, 1H), 8.80 (d, J=2.7 Hz, 1H), 8.65 (s, 1H), 8.39 (dt, J=9.5, 2.2 Hz, 1H), 8.10 (d, 1H), 8.05 (d, 1H), 8.0-6.5 (br s).
0.66 g
With sulfur; 1,10-Phenanthroline; copper(II) choride dihydrate; potassium carbonate; In water; for 16h;Reflux;
Methyl 4-amino-3-iodobenzoate (1.93 g, 6.96 mmol) was combined with K2C03 (1.92g), 8 (668 mg), CuC12-2H20 (119 mg), 1,10-phenanthroline (125 mg) and 5-fluoro-3- pyridinecarboxaldehyde (957 mg) in H20 (30 mL), and the reaction mixture was heated at reflux 16 hours. The cooled reaction mixture was filtered, and the filtrate was treated with NH4C1 (1.49 g). The reaction mixture was stirred at ambient temperature for 10 minutes, filtered, and the solid was dried in vacuo to yield a gray solid. The solid was suspended indioxane, the suspension was heated to reflux, cooled, and filtered to isolate a solid. The solid was rinsed with ethyl ether to give the title compound (0.66 g). ?H NMR (DMSO-d6) oe: 9.15 (s, 1H), 8.80 (d, J=2.7 Hz, 1H), 8.65 (s, 1H), 8.39 (dt, J=9.5, 2.2 Hz, 1H), 8.10 (d, 1H), 8.05 (d, 1H), 8.0-6.5 (br s).
methyl 4-amino-3-((4-(hydroxymethyl)phenyl)ethynyl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In toluene; at 20℃;
A combined suspension of methyl 4-amino-3-iodobenzoate (2,72 g, 9.83 mmol), copper (_) iodide (37 mg, 0.20 mmol), bis(triphenylphosphine)palladium(II) dichloride (138 mg, 0.20 mmol), and tert-butyl((4-ethynylbenzyl)oxy)dimethylsilane (2.91 g, 11.79 mmol) were stirred in toluene and TEA (1/1, 82 mL) at ambient temperature for overnight. The reaction solvent was evaporated under reduced pressure, and the residue was purified by column chromatography with hexane/ethyl acetate (7/1, v/v) to obtain the compound 62 as a brown solid (3.89 g, quant. yield):
methyl 4-amino-3-(1-methyl-1H-pyrazol-4-yl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100%
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; In 1,4-dioxane; water; at 90℃; for 8h;Inert atmosphere;
A suspension of methyl 4-amino-3-iodobenzoate (500 mg, 1.81 mmol), 1 -methyl -4-(4, 4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (563 mg, 2.71 mmol), Pd(dppf)Cl2 (132 mg, 0.18 mmol) and Cs2C03 (1177 mg, 3.61 mmol) in Dioxane/H20 (10 mL/2 mL) was stirred at 90C for 8h under Nitrogen. The mixture was then diluted with H20 (30 mL) and extracted with DCM (30 mL*2). The combined organic phases were concentrated in vacuo and the residue was purified by flash chromatography on silica gel (Petroleum Ether/Ethyl Acetate = 1/1) to afford methyl 4- amino-3-(l-methyl-lH-pyrazol-4-yl)benzoate (417 mg, 100%) as a brown solid. MS Calcd.: 231, MS Found: 232 ([M+H]+).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
