4-AMino-2-chloro-1,3,5-triazine

White Solid

2, 4-dichloro-l, 3, 5-triazine(45 mg, 0.3 mmol) was added to 2 mL of ΝΗ2, 4-dichloro-1, 3, 5-triazine(45 mg, 0.3 mmol) was added to 2 mL of ΝΗ2, 4-dichloro-l, 3, 5-triazine(45 mg, 0.3 mmol) was added to 2 mL of ΝΗ2, 4-dichloro-1, 3, 5-triazine(45 mg, 0.3 mmol) was added to 2 mL of ΝΗTo the solution of 4-chloro-1, 3, 5-triazin-2-amine (5.7 g, 44.0 mmol) in MeOH (100 mL) cooled to 0 was added CH3ONa (35.2 mL, 176.1 mmol, 5.0 M) dropwise. Then the mixture was stirred at room temperature for 1h. Half of the solvent was removed by vacuum, and the precipitate was filtered, washed with water to afford 4-methoxy-1, 3, 5-triazin-2-amine as a white solid (1.0 g) . LC-MS: m/z 127.1 (M+H) +.2, 4-dichloro-l, 3, 5-triazine(45 mg, 0.3 mmol) was added to 2 mL of NuEta4OH aq., the reaction was stirred at -20 C for 10 min, then filtered, washed with water and dried to give 4-chloro- l, 3, 5-triazin-2-amine (18 mg, yield: 46%) as a yellow solid which was used in the next step without further purification. MS (m/z): 131.0 (M+H)+.2, 4-dichloro-1, 3, 5-triazine(45 mg, 0.3 mmol) was added to 2 mL of NuEta4OH aq., the reaction was stirred at -20 C for 10 min, then filtered, washed with water and dried to give 4-chloro- l, 3, 5-triazin-2-amine (18 mg, yield: 46%) as a yellow solid which was used in the next step without further purification. MS (m/z): 131.0 (M+H)+.Method BGeneral conditions for the preparation of 4-chloro-l, 3, 5-triazin-2-amine:[00365] 2, 4-Dichloro-l, 3, 5-triazine (B-1) (500 mg, 3.3 mmol, 1.0 eq) is dissolved in concentrated ammonium hydroxide (100 mL, 700 mmol, 212 eq) at -20 C and the resulting mixture is stirred at this temperature for 10 min. The mixture is then filtered, rinsed with water (5 mL x 3) and dried in vacuo to afford the product, 4-chloro- l, 3, 5-triazin-2-amine (B-2) as a solid.2, 4-dichloro-l, 3, 5-triazine(45 mg, 0.3 mmol) was added to 2 mL of NuEta320 aq., the reaction was stirred at -20 C for 10 min, then filtered, washed with water and dried to give 4-chloro-l, 3, 5-triazin-2-amine (18 mg, yield: 46%) as a yellow solid which was used in the next step without further purification. MS (m/z): 131.0 (M+H)+.2, 4-dichloro-1, 3, 5-triazine (8.0 g, 53.3 mmol) was added in portions to 200 mL of NH4OH at -20 .After addition, the mixture was stirred at -20 for 10mins, and then filtered, washed with water and dried to give 4-chloro-1, 3, 5-triazin-2-amine (5.7 g) as a yellow solid which was used to the next step without further purification. LC-MS: m/z 131.1 (M+H) +.General procedure: A mixture of 1e (30 mg, 0.095 mmol), 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine-5- carbonitrile (22 mg, 0.128 mmol) and TEA (0.05 ml, 0.360 mmol) in n-BuOH (3 mL) was stirred at reflux for 1.5 h. The reaction mixture was concentrated and purified by flash column chromatography eluting with MeOH/DCM to afford Compound 1 as a white solid (29 mg, yield: 64%). 2, 4-dichloro-l, 3, 5-triazine(45 mg, 0.3 mmol) was added to 2 mL of NuEta320 aq., the reaction was stirred at -20 C for 10 min, then filtered, washed with water and dried to give 4-chloro- l, 3, 5-triazin-2-amine (18 mg, yield: 46%) as a yellow solid which was used in the next step without further purification. MS (m/z): 131.0 (M+H)+. (S)-2-(1-(4-amino- l, 3, 5-triazin-2-yl)pyrrolidin-2-yl)-5-chloro-3-phenylpyrrolo[1, 2- f][1, 2, 4]triazin-4(3H)-one was prepared with General procedure: A mixture of 1e (30 mg, 0.095 mmol), 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine-5- carbonitrile (22 mg, 0.128 mmol) and TEA (0.05 ml, 0.360 mmol) in n-BuOH (3 mL) was stirred at reflux for 1.5 h. The reaction mixture was concentrated and purified by flash column chromatography eluting with MeOH/DCM to afford Compound 1 as a white solid (29 mg, yield: 64%). 2, 4-dichloro-l, 3, 5-triazine(45 mg, 0.3 mmol) was added to 2 mL of NuEta320 aq., the reaction was stirred at -20 C for 10 min, then filtered, washed with water and dried to give 4-chloro- l, 3, 5-triazin-2-amine (18 mg, yield: 46%) as a yellow solid which was used in the next step without further purification. MS (m/z): 131.0 (M+H)+. (S)-2-(1-(4-amino- l, 3, 5-triazin-2-yl)pyrrolidin-2-yl)-5-chloro-3-phenylpyrrolo[1, 2- f][1, 2, 4]triazin-4(3H)-one was prepared with EXAMPLE 18N- {( IS)-I - r8-Chloro-2-( pyrrolidin- 1 -vDalphauinolm-3 -yl] ethvU - [1.3.51triazine-2.4-diamine To a solution of Intermediate 38 (44 mg, 0.16 mmol) in 1, 4-dioxane (2 mL) were added 2-amino-4-chloro-[l, 3, 5]triazine (42 mg, 0.32 mmol) and DIPEA (0.06 mL, 0.35 mmol) and the mixture was heated at 12O0C under microwave irradiation for 1 h. The solvent was removed in vacuo and the residue purified by preparative HPLC to afford the title compound (5.4 mg, 9%) as an off-white solid. deltaH (DMSOd6) 8.14-8.00 (IH, m), 7.74-7.62 (2H, m), 7.24-7.14 (IH, m), 6.83-6.73 (2H, m), 5.71-5.61 (IH, m), 3.78 (4H, d, J 17.65 Hz)5 2.52 (2H5 under DMSO)5 2.06-1.94 (4H, s), 1.40-1.33 (3H5 m). LCMS (ES+) 370 (MH-H)+, RT 3.42 minutes.

A metabolite of atrazine (A794600).

Molecular Weight:130.53
XLogP3:0.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:130.0046238
Monoisotopic Mass:130.0046238
Topological Polar Surface Area:64.7
Heavy Atom Count:8
Complexity:77.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes