4-(BOC-AMINO)BUTYL BROMIDE

Off-White Low Melting Solid

tert-Butyl (4-hydroxybutyl)carbamate (1.06 g, 5.788 mmol) was dissolved in dry THF (54 ml) followed by addition of PhTo a solution of tert-butyl (4-hydroxybutyl)carbamate (5a) (1.0 g, 5.3 mmol) and PPh3 (2.09 g, 8 mmol) in 20 mL of THF, a solution of CBr4 (2.7 g, 8 mmol) in 10 mL of THF was added dropwise, under stirring, at 0 °C. The mixture was allowed to warm to room temperature and stirred for 4 h. The solvent was evaporated in vacuo, then the residue was purified by silica gel flash chromatography, eluting with hexanes, then hexanes/ethyl acetate, from 95/5 to 8/2, affording 1.31 g (5.2 mmol, 98percent yield) of pure, target product, as a colorless oil.‘H NMR (400 MHz, CDC13): = 4.54 (bs, 1 H); 3.44 (t, 2 H); 3.17-3.14 (m, 2 H); 1.92-1.87 (m, 2 H); 1.69-1.63 (m, 2 H); 1.46 (s, 9 H).A solution of compound 07-4-1 (11.0 g, 58.1 mmol, 1.0 eq) in DCM (200 mL) were added CBrTo an ice-cold solution of tert-butyl 4-hydroxybutylcarbamate (5 g, 26.41 mmol) in dichloromethane (200 mL) was added triphenylphosphine (10.38 g, 39.61 mmol) followed by carbon tetrabromide (13.15 g, 39.61 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 18 h. The solvent was removed under reduced pressure and the residue was purified by column chromatography (60-120 mesh silica gel) using 10percent ethyl acetate in pet-ether to give tert-butyl 4-bromobutylcarbamate(4.2 g, 63.3 percent) as a light green liquid. 7b) The 5 g 4 - the bromine is positive butane -1 - ammonia hydrobromide with 4.686 g (1.5 eq) carbonic acid di-tert-butyl dicarbonate dissolved in two in the methylene chloride solution, stirring and dissolving, slowly dropping containing 193 mg (0.1 eq) 4 - dimethylamino pyridine and 8.688 g (4 eq) methylene dichloride solution of triethylamine, the reaction at room temperature for 1.5 h. Finally in the separatory funnel for respectively 0.5 N hydrochloric acid aqueous solution and saturated salt water washing the reaction solution, after drying by anhydrous sodium sulfate, filtered, reduced pressure distillation to remove the organic solvent, to obtain 5.387 g intermediate II.EXAMPLE 229 [6-(4-Guanidino-butoxy)-2-oxo-1, 2, 3, 4-tetrahydro-quinolin-3-yl]-acetic acid The title compound was synthesised from (6-hydroxy-2-oxo-1, 2, 3, 4-tetrahydro-quinolin-3-yl)-acetic acid ethyl ester and (4-bromo-butyl)carbamic acid tert-butyl ester in essentially the same manner as described in Example 225 and followed by steps in essentially the same manner as described in Examples 226, 227 and 228. Mp. 170-73 C. IR(KBr): 3420 (s), 1703 (s), 1665 (s), 1432 (m), 1409 (m), 1245 (s), 1195 (s), 1160 (s), 1134 (s), 863 (w), 800 (w), 720 (m), 679 (m) cm31 1. 1H NMR: (DMSO-d6, 400 MHz): delta1.60 (m, 2H, NCH2CH2), 1.69 (m, 2H, OCH2CH2), 2.31 (m, 2H, ArCHH), 2.68-2.91 (overlapping m, 4H, ArCHH, CH, CHHCO2), 3.15 (m, 2H, NCH2), 3.92 (t, J=6 Hz, 2H, OCH2), 6.70-6.78 (overlapping m, 3H, ArH), 6.78-7.54 (broad s, 4H, [C(NH2]+), 7.64 (t, J=6 Hz, 1H, NHCH2), 9.99 (s, 1H, ArNH), 12.2 (broad s, 1H, CO2H). MS (+FAB) m/e (rel. intensity): 335 (M+H, 100).A solution of 4-[6-(4-methyl-l-piperazinyl)-lH-benzimidazol-2-yl]- 2- benzenediamine (50 mg, 0.16 mmol) and 4-hydroxy-3-nitrobenzaldehyde (39 mg, 0.23 mmol) in AcOH (5.0 mL) was heated at 130 C for 3 h. The solvent was removed using a rotavapor. The cmde was purified by column chromatography on silica gel (CHCT : MeOH = 3 : 1) to give Intermediate 1 (22 mg, 18%). Intermediate 1 (20 mg, 42.6 pmol), 4-(Boc-amino)butyl bromide (14 mg, 55.4 frmol), and K2CO3 (15.9 mg, 0.12 mmol) was dissolved in DMF (1 mL). The reaction mixture was stirred for 5h. Solvent was removed using a high vacuum pump via rotary evaporation. The crude was purified by column chromatography on silica gel (CHCb :MeOH = 4 : 1) to give Intermediate 2 (8 mg, 29%).To a solution of 2'-(4-hydroxyphenyl)-5-(4-methyl-l-piperazinyl)-2, 5'-bi(lH- benzimidazole) (28 mg, 66.0 nmol) in DMF (2 mL) were added K2CO3 (25 mg, 0.18 mmol) and 4-(Boc-amino)butyl bromide (21.6 mg, 85.7 mmol), and the reaction mixture was heated at 60 C for 24 h. The solvent was removed using a high vacuum pump via rotary evaporation. The crude was purified by column chromatography on silica gel (CHCI3 :MeOH = 3 : 1) to give an intermediate (15 mg, 38%).To a l-dram vial was added sequentially la (36.7 mg, (1218) 0.200 mmol), AgN03 (135 mg, 0.800 mmol), ammonium persulfate (182 mg, 0.800 mmol), N- bromosuccinimide (NBS: 142 mg, 0.800 mmol) and 1.0 mL of a 1 :9 acetone: H20 solution. The resulting mixture was allowed to stir at room temperature. After 30 min, the reaction mixture was partitioned with EtO Ac (0.5 mL) and fbO (0.5 mL) and the phases were separated. The aqueous phase was extracted with EtO Ac (1.5 mL x 3) and the combined organic layers were concentrated under reduced pressure. The crude residue was purified by preparative thin-layer chromatography (33% EtO Ac/hexanes) to provide A'-(4-broniobutyl)benzamide (4a) (25.4 mg, 54%) as a yellow waxy solid. NMR (400 MHz, CDCb): d 5.67 (s, 1H), 3.43 (t, J= 7.0 Hz, 2H), 3.27 (q, J= 7.0 Hz, 2H), 1.88 (quint, J= 7.0 Hz, 2H), 1.66 (quint, J= 7.0 Hz, 2H), 1.19 (s, 9H); 13C NMR (l 5l MHz, CDCh) d 178.7, 38.8, 38.7, 33.5, 30.2, 28.5, 27.8; HRMS (ESI): Calc'd for CsHisBrNNaO [M+Na]+: 258.0464, found: 258.0459.The synthesis of this monomer proceeds by alkylation of WAY-600 (CAS 1062159-35-6) with

Molecular Weight:252.15
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:6
Exact Mass:251.05209
Monoisotopic Mass:251.05209
Topological Polar Surface Area:38.3
Heavy Atom Count:13
Complexity:154
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes