5-AMINO-4-CHLOROPYRIMIDINE

To the product of (4.3 g, 26 mmol) dissolved in conc. NHTo the product of Example 20 (4.3 g , 26 mmol) dissolved in cone. NHTo the product of (4.3 g , 26 mmol) dissolved in cone. NH (4.00 g, 30.9 mmol.) is dissolved in room temperature water (200 mL), and then cooled to about '5 to 0° C. in a salt/ice bath. An oxidizing solution (bleach about 10percent-136 sodium hypochlorite, 126 mL, 204 mmol. (a stoichiometric molar ratio of sodium hypochlorite:4-Chloro-5-aminopyrimidine (156 mg, 1.2 mmol) and(S)-3-tert-Butoxycarbonylaminopyrrolidine (268 mg, 1.44 mmol) was dissolved in 8 mL of methanol.Add DIPEA (186 mg, 1.44 mmol), Stir at reflux and TLC was monitored until the reaction was complete.The reaction solution was concentrated under reduced pressure. EtOAc (EtOAc)The combined organic layers were washed with EtOAc EtOAc m.The residue was purified by TLC (dichloromethane:methanol = 20:1).Obtained as a yellowish brown oily liquid(S)-1-(5-Aminopyrimidin-4-yl)pyrrolidin-3-yl-carbamic acid tert-butyl ester (262 mg, 78percent).The 5-amino-6-chloropyrimidin-4(1H)-thione hydrochloride compound (2.67 g) was dissolved in 25 mL of dry methanol.Add 25percent ammonia (2.5 mL) and Raney Ni (2 mL).Stir at 80 ° C under a nitrogen atmosphere, and the reaction was completed by TLC.The reaction solution was filtered, and the filter cake was washed with methanol, and the filtrate was concentrated under reduced pressure.4-Chloro-5-aminopyrimidine (156 mg, 9.9percent) was obtained as a yellow solid.Step 1 : To a 50mL round -bottom flask was added 20mL 1, 4-Dioxane, compound 5a (885mg, 6.83mmol, l .Oeq), compound lb (1.61g, 7.52mmol, l. leq) and DIPEA (1.32g, 10.25mmol, 1.5eq). The reaction was heated to reflux for 18h. TLC (PE: EA= 1 : 1) showed the reaction was completed. The reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel eluted with PE: EA= 3 : 1- 1 : 1 to afford the title compound 5b (1.5g, HPLC: 93%, Yield: 71.4%) as an orange solid.0058] At room temperature, NaH (67 mg, 2.79 mmol) was added to a solution of tert-butyl 4-(hydroxymethyl) piperidine-1-carboxylate (131) (500 mg, 2.32 mmol) in THF (tetrahydrofuran) (10 mL) and stirred for 1 hour. 4-chloro-pyrimidin-5-amine (A) (346 mg, 2.67 mmol) was then added. The reaction mixture was then heated to 100°C under nitrogen and stirred for 4 hours, cooled to room temperature (20-30°C) and concentrated in vacuo. The residue was purified with flash column (eluent: 10-30percentethyl acetate/petroleum ether) to obtain the product C1 (308mg, 1.0 mmol).A mixture of To a stirred solution of

Molecular Weight:129.55
XLogP3:0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:129.0093748
Monoisotopic Mass:129.0093748
Topological Polar Surface Area:51.8
Heavy Atom Count:8
Complexity:77.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes