5-Amino-thiophene-2-carboxylic acid methyl ester

To methyl 5-nitro-2-thiophenecarboxylate (11.55 mmol) in ethyl alcohol (20 mL) was added palladium on carbon (10percent, 1 g). The reaction mixture was hydrogenated with an atmosphere of H2 overnight. Methyl 5-amino-2-thiophenecarboxylate (1.67 g, 92percent) was obtained after filtration and concentration.LCMS (ESI) 157 [MH-H]Part A To a mixture of 2-nitrothiophene (600 mg, 3.2 mmol) and SnClSynthesis of 4-[dimethylamino)diazenyl]thiophene-2-carboxamide (compound 12); Step a:4-Nitrothiophene-2-carboxylic acid: Sulfuric acid (3.0 mL, 5.505 g, 56.17 mmol) was added to nitric acid (2.0 mL, 2.98 g, 49.6 mmol) slowly at 0-10 To methyl 5-nitro-2-thiophenecarboxylate (11.55 mmol) in ethyl alcohol (20 mL) was added palladium on carbon (10%, 1 g). The reaction mixture was hydrogenated with an atmosphere of H2 overnight. Methyl 5-amino-2-thiophenecarboxylate (1.67 g, 92%) was obtained after filtration and concentration.LCMS (ESI) 157 [MH-H]+.Part A To a mixture of 2-nitrothiophene (600 mg, 3.2 mmol) and SnCl2.2H2O (4.86 g, 25.6 mmol) in 95% EtOH(13.6 mL) was added concentrated HCl (13.6 mL) dropwise at room temperature (sufficient cooling was necessary to keep the reaction temperature under 35 C.). After the addition, the reaction mixture was stirred at 35 C. for 2 hours. EtOH was removed under vacuum and the aqueous layer was washed with hexane (50 mL×2). The pH of the aqueous layer was adjusted to pH 9 and was extracted three times with EtOAc (50 mL). The extracts were combined and dried over Na2SO4. After evaporation of solvent, the product was obtained as white solid (332 mg, 66%). 1H NMR (400 MHz, DMSO-d6): 7.15(d, 1H), 6.60(s, 2H), 5.10(d, 1H), 3.65(s, 3H). LC-MS m/z 158.1 (M+H).To a solution of the above synthesized methyl 5-nitro-2-thiophenecarboxylate (2.67 g, 14.3 mmol) and iron (2.63 g, 47.1 mmol) in ethanol (50 ml) and water (9.9 ml), concentrated hydrochloric acid (0.12 ml, 1.43 mmol) wasadded at 90C. And the mixture was stirred at 90C for 30 minutes. After completion of the reaction, 1 M sodium hydroxide aqueous solution (1.43 ml, 1.43 mmol) was added thereto. The insolubles were filtered off, and the filtrate was concentrated and extracted with ethyl acetate, then dried over anhydrous sodium sulfate. The obtained organic layer was concentrated and dried by means of a vacuum pump. From the resulting crude solid, the desired product was obtained in the same manner as in Reference Synthetic Example 56 as a pale yellow oil (904 mg, yield 32%). ^-NMR (ppm in CDC13)8 7.56 (d, J= 4.0 Hz, 1H), 6.83 (d, J= 4.0 Hz, 1H), 3.88(s, 3H). LC/MS (ES+) 199To a stirred solution of 96 (35 g; 187 mmol) in MeOH (400 ml) was added a suspension of 10% palladium on carbon (30 g) in [ACOH] (100 ml) The resulting suspension was exposed to 1 atmosphere of hydrogen for 8 hours after [WHICH HPLC] showed no remaining starting material. The catalyst was removed by filtration through a pad of Celite and the filtrate was evaporated to dryness and the residue purified by flash chromatography on silica gel eluting with DCM-MeOH (98: 2) to afford the amine (11.4 g) as an off-white solid, which was used immediately in the next step. To a stirred solution of the amine (11.4 g; 72.9 mmol) in THF (20 ml) was added di-tert-butyldicarbonate [( (BOC) 20)] (17.5 g; 80.2 mmol). The resulting solution was heated to reflux for 3 days after which HPLC showed no remaining starting material. The reaction mixture was evaporated to dryness and the residue obtained was triturated with diethyl ether (100 ml). The resulting precipitate was collected by filtration, washed with diethyl ether [(2X50] ml) and dried to a constant weight to afford 97 (15.1 g) as an off-white crystalline solid. Yield: 32% MS-ESI: 258 [[M+H] +] [1H] NMR [(DMSO-D6)] 1.53 (s, 9H), 3.74 (s, 3H); 6.55 (d, 1H) ; 7.57 (d, 1H).Preparation of 5-Aminothiophene-2-carboxylic acid methyl ester (39).; To a solution of 5.0 grams of 5-nitro-thiophene-2-caroboxylic acid methyl ester (38, 26.7 mmol) in 50 mL of MeOH and 25 mL of THF was added 1.0 g of Pd(OH)2 (20 wt % on carbon, wet). The mixture was placed on a Parr shaker at 55 psi H2 and shaken overnight. The mixture was filtered through Celite and the solvent was removed by rotary evaporation. The residue was dissolved in EtOAc and washed with sat. aq. NaHCO3. The organic layer was dried over Na2SO4, filtered, and the solvent was removed by rotary evaporation to afford the product as a brown solid.Step A: To a solution of nitroester (2285 mg, 12.22 mmol) in HOAc (55 mL) was added iron powder (6825 mg, 122.20 mmol). The reaction mixture was heated at 75C for 10 min. The mixture was cooled to room temperature and then added 200 mL of MeOH. The resulting mixture was filtered through celite (the celite was rinsed with additional amount MeOH). The filtrate was concentrated to remove most of AcOH. To the residue was added 50 mL of 20% MeOH/CH2CI2 followed by saturated Compounds of Formula 5: ... 2-amino-thiophene-4-carboxylic acid; methyl 2-amino-thiophene-4-carboxylate; ethyl 2-amino-thiophene-4-carboxylate; 2-amino-thiophene-5-carboxylic acid;

Molecular Weight:157.19
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:157.01974964
Monoisotopic Mass:157.01974964
Topological Polar Surface Area:80.6
Heavy Atom Count:10
Complexity:140
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes