2-AMINO-THIAZOLE-4-CARBOXYLAMIDE

3.0 g Ethyl 2-aminothiazol-4-carboxylate was added to 100 ml ammonia water, reacted for 2 hr, concentrated, and placed aside to precipitate a needle crystal, which was filtered, washed with water, and dried to obtain 1.9 g 2-aminothiazol-4-carboxamide (yield 76percent) with mp 208-211°C.3.0 g Ethyl 2-aminothiazol-4-carboxylate was added to 100 ml ammonia water, reacted for 2 hr, concentrated, and placed aside to precipitate a needle crystal, which was filtered, washed with water, and dried to obtain 1.9 g 2-aminothiazol-4-carboxamide (yield 76percent) with mp 208-211° C.A solution of 2-amino-thiazole-4-carboxylic acid ethyl ester (258 mg, 1.5 mmol) (prepared as described in example 3, step 1) in concentrated aqueous ammonium hydroxide was heated to reflux for 8 hours. The reaction mixture was concentrated to dryness and residual water removed by azeotropic distillation with toluene. The residue was purified by chromatography over silica gel eluted with 2percent v/v methanol in ethyl acetate to give 2-amino-thiazole-4-carboxylic acid amide as a colorless solid (149 mg, 69percent). LR-MS: Obs. Mass, 143.0. Calcd. Mass, 143.0153 (MTo a solution of 2-chloro-6-(trifluoromethyl)benzo[d]oxazole (500 mg, 2.26mmol) in DMF (8.0 mL) were added General procedure: To a solution of tert-butyl (4-(methylcarbamoyl)thiazol-2-yl)carbamate (1 .2g, 4.6mmol) in DCM (35mL) was added TFA (l2mL) dropwise at rt. The reaction mixture was stirred at rt for 3 h. The TLC showed the reaction to be complete. The solvent was removed under reduced pressure. The residue obtained was basified to pH 8 with aq. NaHCO3 solution and extracted with EtOAc (3x5OmL). The organic layer was washed with brine (5OmL), dried (Na2504), filtered and concentrated under vacuum to afford 2-amino-N-methylthiazole-4-carboxamide as a yellow solid. Yield: 600mg (82%); 1H NMR (400 MHz, DMSO-d6): 7.74 (bs, 1H), 7.14 (5, 1H), 7.03 (bs, 2H), 2.71 (bs, 3H); MS (ESl+) for CHNOS m/z 158.04 [M+H].Step 3: Synthesis of 3-[1-(4-Carbamoyl-thiazol-2-yl)-5-(4-methoxy-phenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester (1C, R1=4-carbamoyl-thiazol-2-yl, R2=4-methoxy-phenyl) (0161) To a solution of 7-(4-methoxy-phenyl)-4, 7-dioxo-heptanoic acid ethyl ester (0.5 mmol), see scheme 1, in ethanol (2 mL) were added the amine (1.5 equivalents) and p-toluenesulfonic acid monohydrate (0.5 eq.). The reaction was run using the Biotage Microwave Initiator for 1 to 3 hours at 150 C. The solvent was removed in vacuo to obtain the crude mixture which was purified by prep silica gel plate to obtain the final product (70 mg, 38%).4. g (28 mmol) 2-Aminothiazol-4-carboxamide was dissolved in 40 ml glacial acetic acid, to which added 2.8 ml (29.6 mmol) acetic anhydride, followed by reacting under reflux for 2 hr, and naturally cooling down to precipitate a large quantity of solids, which were filtered, washed and dried to obtain 4.7 g 2-acetylaminothiazol-4-carboxamide (yield 92%) with mp >250C.4. g (28 mmol) 2-Aminothiazol-4-carboxamide was dissolved in 40 ml glacial acetic acid, to which added 2.8 ml (29.6 mmol) acetic anhydride, followed by reacting under reflux for 2 hr, and naturally cooling down to precipitate a large quantity of solids, which were filtered, washed and dried to obtain 4.7 g 2-acetylaminothiazol-4-carboxamide (yield 92%) with mp>250 C.To a solution of 2-(S)-(2-tert-butoxycarbonylamino-2-phenyl-acetylamino)-3-phenyl-propionic acid (239 mg, 0.6 mmol) and 3.0 g Ethyl 2-aminothiazol-4-carboxylate was added to 100 ml ammonia water, reacted for 2 hr, concentrated, and placed aside to precipitate a needle crystal, which was filtered, washed with water, and dried to obtain 1.9 g 3.0 g Ethyl 2-aminothiazol-4-carboxylate was added to 100 ml ammonia water, reacted for 2 hr, concentrated, and placed aside to precipitate a needle crystal, which was filtered, washed with water, and dried to obtain 1.9 g A solution of 2-amino-thiazole-4-carboxylic acid ethyl ester (258 mg, 1.5 mmol) (prepared as described in example 3, step 1) in concentrated aqueous ammonium hydroxide was heated to reflux for 8 hours. The reaction mixture was concentrated to dryness and residual water removed by azeotropic distillation with toluene. The residue was purified by chromatography over silica gel eluted with 2% v/v methanol in ethyl acetate to give

Molecular Weight:143.17
XLogP3:-0.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:143.01533297
Monoisotopic Mass:143.01533297
Topological Polar Surface Area:110
Heavy Atom Count:9
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes