5-chloro-3-methylsulfanyl-2,4,9-triazabicyclo[4.3.0]nona-2,4,7,10-tetraene

POCl3 (5 mL, 53.7 mmol) and triethylamine (0.2 mL, 1.43 mmol)were added to 2-(methylthio)-7H-pyrrolo[2, 3-d]pyrimidin-4-ol 10(0.10 g, 0.55 mmol); the mixture was heated at 130° C for 4h andthen cooled to room temperature. The excess of POCl3 was removedby distillation under reduced pressure. Icewas then carefully addedto the residue and the suspension was extracted with diethyl ether(3 20 mL). The organic phasewaswashed with H2O (10 mL), driedon MgSO4, filtered and concentrated under reduced pressure. Thecrude was purified by column chromatography (Florisil®, 100e200mesh), using diethyl ether as the eluent to afford the pure product4-chloro-2-(methylthio)-7H-pyrrolo[2, 3-d]pyrimidine (77percent, lit.43percent) [33]. Mp: 207-209° C. 1H NMR (CDCl3): δ2.67 (s, 3H, SCH3), 6.56-6.59 (m, 1H, H-5), 7.21-7.23 (m, 1H, H-6). IR (KBr) cm-1: 3412(NH), 3122 (CH), 1614 (C=C). MS: m/z [M+1]+ 201. Anal. calcd. forC7H6N3ClS, C 42.11, H 3.03, N 21.05, S 16.06, found C 42.29, H 3.38, N21.14, S 16.36.A solution of (35n) (200.0 mg, 1.0 mmol) in acetonitrile (5 mL) was supplemented with (1/?, 25)- 2-(3, 4-difluorophenyl)cyclopropanamine (340.0 mg, 2.0 mmol) and triethylamine (0.30 mL) and then heated at 90C under reflux for 1 h. After distillation of acetonitrile and triethylamine under vacuum, the residue was purified by silica gel column chromatography.Yield: 15%.Melting point: 208-211C.H NMR (DMSO -d6) d 1.34 (m, 2H, NHCH(CH2)CHPh), 2.03 (s, 1H, NHCH(CH2)CHPh), 2.30 (s, 3H, S CH3), 3.03 (s, 1H, NHCH(CH2)CHPh), 6.40 (s, 1H, 5 -H), 6.93 (s, 1H, T-H), 7.08 (s, 1H, S'-H), 7.33 (m, 2H, S-H/S'-H), 7.84 (s, 1H, NHCH(CH2)CHPh), 11.40 (s, 1H, N H).13C NMR (CDCI3) d 13.3 (SCH3), 99.5 (C-5), 112.1 (C-4a), 117.0 (C-5'), 119.9 (C-2'), 122.9 (C-6'), 139.6 (C-l'), 147.0-148.3 (C-4'), 148.6-150.0 (C-3'), 162.3 (C-2).700 mg of 2-(methylthio)-3, 7-dihydro-4H-pyrrole[2, 3-d]pyrimidine-4-one obtained in Step 3 was heated to reflux overnight in 10 ml of phosphorus oxychloride. The reaction solution was concentrated on the next day, diluted with water, extracted with ethyl acetate, and the organic phase was washed with saturated sodium chloride and dried over anhydrous sodium sulfate, and then concentrated to dryness to give 4-chloro-2-(methylthio)-7H-pyrrole[2, 3-d]pyrimidine. 1H NMR (300 MHz, DMSO-d6) delta 12.40 (s, 1H), 7.52 (d, J = 3.4 Hz, 1H), 6.51 (s, 1H), 2.55 (s, 3H).100 mg of above prepared 4-chloro-2-(methylthio)-7H-pyrrole[2, 3-d]pyrimidine and 146 mg of N-iodosuccinimide were dissolved in 2 ml of N, N-dimethylformamide, and stirred at room temperature for 18 hours. The reaction mixture was diluted with water, and a large amount of solids were precipitated, dried and filtered to give 140 mg of purple solids, yield 91%. 1H NMR (300 MHz, DMSO-d6) delta 12.72 (s, 1H), 7.75 (s, 1H), 2.55 (s, 3H).Sodium hydride (60% dispersion in mineral oil, 0.1 g, 2.5 mmol)was slowly added to a solution of 4-chloro-2-(methylthio)-7Hpyrrolo[2, 3-d]pyrimidine 11 (0.19 g, 1 mmol) in anhydrous acetonitrilefreshly distilled (5 mL) and the mixture was stirred at roomtemperature for 20 min. Then 4-fluorobenzyl chloride (0.14 g, 1 mmol) solved in anhydrous acetonitrile (5 mL) was added dropwise.The mixture was heated at 50 C for 2h, then cooled to roomtemperature and filtered to eliminate the little amount of solidobtained. The solution was then evaporated under reduced pressureand the crude was purified by column chromatography (Florisil, 100-200 mesh), using diethyl ether as the eluent to affordpure 4-chloro-7-(4-fluorobenzyl)-2-(methylthio)-7H-pyrrolo[2, 3-d]pyrimidine 15 as light yellow solid (36%). Mp: 99-100 C. 1H NMR(CDCl3):delta 2.65 (s, 3H, SCH3), 5.36 (s, 2H, CH2N), 6.53 (d, J = 3.6, 1H, H-5), 6.96-7.04 and 7.14-7.24 (2m, 5H, 4Ar H-6). MS: m/z[M+1]+ 309. Anal. calcd. for C14H11N3ClFS, C 54.63, H 3.60, N 13.65, S 10.42, found C 54.41, H 3.69, N 13.42, S 10.15.Sodium hydride (60% dispersion in mineral oil, 0.04 g, 1 mmol)was added in small portions at 0 C to a solution of

Molecular Weight:199.66
XLogP3:2.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:198.9970961
Monoisotopic Mass:198.9970961
Topological Polar Surface Area:66.9
Heavy Atom Count:12
Complexity:169
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes