2-Aminothiazole-4-carbonitrile

To a DMF (5 mL) solution of (frans)-3-(quinolin-8-yloxy)cyclobutanecarboxylic acid (Intermediate 79) (150 mg, 0.617 mmol) was added HATU (281 mg, 0.740 mmol) and N, N- diisopropylethylamine (0.32 mL, 1 .9 mmol). After 5 minutes, 2-Aminothiazole-4-carbonitrile (1.40 g, 11.18 mmol) was dissolved in 20 mL AcOH in a 150 mL round bottom flask. Br2 (1.78 g, 11.18 mmol) was added to the reaction in a dropwise manner. After stirring at room temperature for 10 minutes, AcOH was removed under vacuum. Saturated sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine and dried over sodium sulfate. 2-amino-5-bromothiazole-4-carbonitrile (1.20 g, yield: 53%) was obtained. LCMS (API-ES) m/z (%): 205.9 (100%, M++2H).Bromoacetyl bromide (15.0 g, 74.3 mmol) was added dropwise into trimethylsilyl cyanide (8.85 g, 89.2 mmol). After addition, the reaction mixture was heated to 70 C. for 90 minutes. 50 mL ACN was added to the reaction and then thiourea (6.78 g, 89.16 mmol) was added to the reaction. The reaction was completed after a 2 hour reflux time. Saturated sodium bicarbonate was added to the reaction mixture, and the reaction mixture was extracted with EtOAc (2×100 mL). The organic layers were combined, washed with brine, and dried over sodium sulfate. No further purification was necessary. LCMS (API-ES) m/z (%): 126.2 (100%, M++H).2-Amino-4-cyanothiazole STR83 Ethyl 1, 2-dihydro-2-ethoxy-1-quinolinecarboxylate (6.68 g, 27.0 mmol) was added to a solution of ethyl [2-(tritylamino)thiazol-4-yl]-(Z)-hydroxyiminoacetate (11.46 g, 26.7 mmol) in N, N-dimethylformamide (100 mL) and stirred for 6 h at room temperature. The reaction was poured into ethyl acetate, washed with 1N hydrochloric acid (2*), water (3*) and brine, dried over sodium sulfate, filtered and concentrated. The resulting white foam (9.9 g) was dissolved in dichloromethane (300 mL), treated with triethylsilane (12.44 g, 107 mmol, 17 mL) and trifluoroacetic acid (25 mL) and stirred for 2.5 h at room temperature. The reaction was concentrated in vacuo, dissolved in ethyl acetate, washed with saturated sodium bicarbonate solution and brine, dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (1:1 ethyl acetate and hexanes) to provide 2.75 g (82%) of the title product as a white solid: mp 154-156 C.; IR (KBr, cm-1) 3416, 3291, 3118, 2234, 1638, 1547, 1315, 1108; 1 H NMR (300 MHZ, CDCl3) delta7.23 (s, 1H), 5.19 (br s, 2H); MS (FD) m/e 125 (M+);

Molecular Weight:125.15
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:125.00476828
Monoisotopic Mass:125.00476828
Topological Polar Surface Area:90.9
Heavy Atom Count:8
Complexity:127
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes