4-Amino-2-trifluoromethylpyridine

3) To a stirred solution of 4-nitro-2-trifluoromethyl-pyridine 1-oxide (0.4 g, 1.90 mmol) in EtOH (15 mL) is added 10percent Pd-C (0.04 g) under nitrogen atmosphere. Hydrogenation is performed in a Parr shaker at 30 psi for 3 h at room temperature. After completion of reaction it is filtered through diatomaceous earth and washed with EtOH. Filtrate is concentrated to give 2-trifluoromethyl-pyridin-4-ylamine as a thick liquid (0.23g, 74percent).Method 29 Preparation of Intermediate Compound (29)--4-Amino-6-trifluoromethylpyridine To a stirred solution of 2-(trifluoromethyl)pyridin-4-ol (4.7 g) in N, N-dimethylacetamide (50 mL) was added potassium carbonate (9.96 g) followed by the addition of 2-chloro-acetamide (3.23 g) at room temperature. The reaction mixture was heated to 90°C and continued stirring at the same temperature for 3 hours. The reaction temperature was further increased to 150°C and allowed to stir at the same temperature for 3 hours. The reaction mixture was partitioned between water and t-butylmethylether TBME. The organic layer was separated and the aqueous layer was re-extracted twice with TBME. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure to afford 2-(trifluoro-methyl)pyridin-4-amine (10-A) as a yellowish oil (3.97 g). The sample generated with Method-B showed the same analytical data as the one produced with Method-A.2-(Trifluoromethyl)pyridin-4-amine (135 mg, 0.83 mmol), DMAP (10.25 mg, 0.08 mmol), BOC20 (274.80 mg, 1.25 mmol) and Et3N (152.83 m, 1.09 mmol) were suspended in anhydrous DCM (3 mL) at rt, and stirred 2 h under argon atmosphere. The reaction mixture was diluted with CH2C12 (25 mL) and washed with 0.1 N HC1 (5 mL). The combined organic layers were dried over anhydrous MgS04 and concentrated under reduced pressure. The obtained residue was taken to the next step without further purification. 'H-NMR (300 MHz, CDC13): d [ppm] = 8.53 (d, J= 5.6 Hz, 1 H), 7.78 (d, J = 2.0 Hz, 1 H), 7.44 (dd, J = 5.5 Hz, 2.1 Hz, 1 H), 6.92 (bs, 1 H), 1.53 (s, 9 H). LC.MS: m/z 207 (M+H-/Bu)+.To a solution of 2-trifluoromethyl-4-aminopyridine (3.24 g, 20.0 mmol) in DCM (60 mL) were added Boc20 (9.82 g, 45.0 mmol), DIPEA (7.66 mL, 44.0 mmol) and DMAP (806 mg, 6.60 mmol). The reaction mixture was stirred for 18 h at r.t. and saturated NHUCl solution was added followed by extraction with EtOAc. The combined organic layers were washed with Brine, dried over Na2S04, filtrated and evaporated under reduced pressure. The crude product was used without any further purification. (0193) LC-MS: m/z: 363 (M+H)+. 1H-NMR (300 MHz, CDC13): d [ppm] = 8.72 (d, J = 5.4 Hz, 1 H), 7.52 (d, J = 1.7 Hz, 1 H), 7.31 (dd, J = 5.3 Hz, J = 1.8 Hz, 1 H), 1.47 (s, 18 H).

Molecular Weight:162.11
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Exact Mass:162.04048265
Monoisotopic Mass:162.04048265
Topological Polar Surface Area:38.9
Heavy Atom Count:11
Complexity:134
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes