2-Chloro-4,5-pyrimidinediamine

To a solution of compound 21-2 (20 g, 114.6 mmol) in EtOH/HStep-1: 2-chloropyrimidine-4, 5-diamine [0176] A mixture of 2-chloro-5-nitropyrimidin-4-amine (1.0 g, 5.7 mmol) and SnClDIPEA (0.35 mL, 2.03 mmol) was added to a stirred suspension of 2-chloro-4, 5- diaminopyrimidine (100 mg, 0.69 mmol), trans-(2S)-2-(tert-butoxycarbonylamino)-2-(4- methylcyclohexyl)acetic acid (271 mg, 0.99 mmol) and HATU (410 mg, 1.08 mmol) in DCM (5 mL) at 20C. The reaction mixture was stirred at 20C for 18 h, then diluted with DCM (15 mL) and washed with saturated aqueous NaHCO3 solution (10 mL). The organic layer was filtered through a hydrophobic frit, and the solvent was concentrated in vacuo. The resulting dark brown oil was dissolved in EtOH (10 mL), and K2CO3 (398 mg, 2.88 mmol) was added. The suspension was heated at 80C in a sealed vial for 40 h. After cooling, the mixture was diluted with water (10 mL), and the aqueous layer was extracted with DCM (3 x 15 mL). The combined organic extracts were filtered through a hydrophobic frit, and the solvent was concentrated in vacuo. The resultant dark brown oil was separated by flash column chromatography, eluting with EtOAc/heptane (0-50% gradient), to afford the title compound (80 mg, 30%) as a yellow oil that slowly solidified on standing. dH (250 MHz, CDCl3) 11.73 (br s, 1H), 8.90 (s, 1H), 5.87-5.64 (m, 1H), 4.74-4.62 (m, 1H), 1.75-1.68 (m, 4H), 1.41 (s, 9H), 1.28-1.04 (m, 6H), 0.88-0.84 (m, 3H). LCMS (Method 10): [M+H]+ m/z 380 and 382, RT 1.18 minutes.Compound 21-3 (4 g, 27.6 mmol) and compound 21-3-1 (5.2 g, 31.2 mmol) were dissolved in HCl/i-PrOH (2 mL/40 mL), and the mixture was heated to 100 C. and stirred for 14 h, followed by adjusted to pH 9 with Na2CO3 (aq.) and extracted with DCM (50 mL×4). The organic phase was dried over anhydrous Na2SO4, filtered and concentrated to give a crude product which was purified by column chromatography to afford compound 21-4 (1.1 g, Yield 14.7%) as black solid.A neat mixture of Step-2: 2-chloro-7H-purin-8(9H)-one [0177] To a solution of (3) To a solution of the above-mentioned product (22.0 g) in pyridine (100 ml) was added dropwise ethyl chloroformate (21.7 ml) at 0 C. and the mixture was stirred at room temperature for 3 hours. To the reaction mixture was added water (300 ml) and the mixture was extracted with ethyl acetate (500 ml*3). The organic layer was dried over anhydrous magnesium sulfate and was filtered, and the solvent was then evaporated under reduced pressure to give the crude solids. The obtained crude solids were recrystallized from a mixture solution of ethyl acetate and hexane to give ethyl (4-amino-2-chloropyrimidin-5-yl)carbamate 21.0 g. 1H-NMR (CDCl3) delta: 1.32 (3H, t, J=7.1 Hz), 4.24 (2H, q, J=7.1 Hz), 5.50 (2H, br s), 6.18 (1H, br s), 8.06 (1H, s).Example 133[2-(4-Dimethylamino-piperidin-1-yl)-9H-purin-8-yl]-(2-isoquinolin-4-yl-pyridin-4-yl)- methanoneStep 1 : A toluene suspension of 2-chloro-pyrimidine 4, 5-diamine (289 mg, 2.0 mmol), trimethylorthoformate (1.9 g, 18 mmol) and benzenesulfonic acid (14 mg, 0.08 mmol) was heated at reflux overnight. The reaction was cooled and diisopropylethylamine (28 Dl, 0.08 mmol) was added. The mixture was evaporated to dryness and the 2-chloro-9-dimethoxymethyl-9H-purine was used without further purificationIntermediate 82: Mixture /V-(5-amino-2-chloro-4-pyrimidinyl)-2-oxo-3-phenyl-1-oxa-3- azaspiro[4.51decane-8-carboxamide and lambda/-(4-amino-2-chloro-5-pyrimidinyl)-2-oxo-3- phenyl-1-oxa-3-azaspiro[4.51decane-8-carboxamide; (Trans^-oxo-S-phenyl-i-oxa-S-azaspiro^.deltaJdecane-delta-carboxylic acid (Intermediate 10 alternative preparation, 239 mg, 0.286 mmol), (a) 8-(2-Methoxy-4-benzyloxy-phenyl)-2-chloro-purine Prepared analogously to Example 5 from

Molecular Weight:144.56
XLogP3:0.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Exact Mass:144.0202739
Monoisotopic Mass:144.0202739
Topological Polar Surface Area:77.8
Heavy Atom Count:9
Complexity:98.6
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes