4-CHLORO-3-FLUOROBENZYLAMINE

Step A. Preparation of tert-butyl ((2-chloro-6-((4-chloro-3-fluorobenzyl)carbamoyl)pyridin-4-yl)methyl)carbamate The title compound was prepared from the procedure described in Example 72, Step D using 4-(((tert-butoxycarbonyl)amino)methyl)-6-chloropicolinic acid and A mixture of Example 235G (40.0 mg, 0.112 mmol), HATU (1- [bis(dimethylamino)methylene]-lH-l , 2, 3-triazolo[4, 5-]pyridinium 3-oxid (1666) hexafluorophosphate) (51.0 mg, 0.134 mmol), To a solution of To a solution of A mixture of Example 477A (61.7 mg, 0.128 mmol), (4-chloro-3- fluorophenyl)methanamine (0.019 mL, 0.153 mmol), and triethylamine (0.021 mL, 0.153 mmol) in N, N-dimethylformamide (1.5 mL) was heated at 50 C for 3 hrs. After cooling, the reaction mixture was treated with brine and extracted with ethyl acetate (2x). The combined organic layers were dried over MgSO/t, filtered, and concentrated. The residue was purified by reverse- phase HPLC (see protocol in Example 112D) to provide the title compound (23.7 mg, 35%).JH NMR (400 MHz, DMSO- General procedure: A mixture of 0.55mmol of 8-bromo-7-(2-bromoethyl)theophylline 7a or 8-bromo-7-(3-chloropropyl)theophylline 7b or 8-bromo-7-(4-bromobutyl)theophylline 7c, 1.1mmol of appropriate aromatic amine, 1, 6 mmol of TEBA and 1.00ml of propanol was heated in closed vessels in microwave oven (300 Watt, Power Max Off, 160C, 10bar) for 1h. The solvent was removed and the residue was treated with ethanol. The products were purified by crystallization from ethanol or flash column chromatography over silica gel with CH2Cl2 : MeOH (100 : 0 to 80 : 20). The precipitate was filtered off and dried.To a solution of General procedure: To a solution of bis(carboxymethyl)trithiocarbonate (0.22 mmol) in DME (1.0 mL) were added TEA (0.22 mmol) andthe opportune amine (0.22 mmol). The reaction mixture was heated at 90C for 10 min undermicrowave irradiation. After this time, the aldehyde 6 (0.22 mmol) was added, and the mixturewas heated at 110C for 5 min under microwave irradiation. The reaction mixture was evaporatedto dryness and the residue was additioned with MeOH and a drop of HCl 2N; the finalrhodanine derivatives were obtained as a pure precipitate, isolated by filtration, washed withwater and hexane, and finally dried under high vacuum. (Z)-4-(5-((3-(4-fluorophenethyl)-4-oxo-2-thioxothiazolidin-5-ylidene)methyl)furan-2-yl)-2-hydroxybenzoic acid (9a). (yield: 30%); Yellow solid. Mp = 292C (decomposition),

Molecular Weight:159.59
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:159.0251051
Monoisotopic Mass:159.0251051
Topological Polar Surface Area:26
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes