Benzenamine, N-[[2-chloro-3-[(phenylamino)methylene]-1-cyclohexen-1-yl]methylene]-, hydrochloride (1:1)

At 0C, phosphorus oxychloride (11.0 ml, 120 mmol) was added dropwise from a pressureequalizingfunnel to anhydrous DMF (13.0 ml, 170 mmol) with stirring. After 30 min, cyclohexanone(5.50 ml, 53.0 mmol) was added and the mixture was heated under reflux for 1 h. Thereaction was cooled to 20C and with stirring, a mixture of aniline/EtOH [1:1 (v/v), 180 ml] wasadded dropwise to the reaction mixture. The reaction was continued for 30 min at 20C with vigorousstirring, and then the deep purple mixture was poured into H2O/HCl [10:1 (v/v), 110 ml].Crystals were allowed to form for 2 h in an ice bath. The reaction was filtered, washed with coldH2O and Et2O, and then dried in vacuo to yield 2 (14.8 g, 97percent) as a dark purple solid. 1H NMR(d6-DMSO, 250 MHz) δ 11.2 (s, 2H, NH), 8.55 (d, J = 14.0 Hz, 2H, CHalkene), 7.68 (d, J = 5.0 Hz4H, Ar-H), 7.44 (t, J = 7.0 Hz 4H, Ar-H), 3.03 (t, J = 6.0 Hz, 4H, CH2-CH2), 2.05–1.98 (m, 2H, CH2-CH2). IR (ATR) 1609 (C=N), 1562, 1457, 1267, 1179, 752, 683, 565 cm−1. MS (ESI) m/z:323.22 [M+]. Mp 226–231C.Anhydrous DMF (13 mL, 0.17 mol) was placed in a 100 mL three-necked flask and cooled to 0° C. Phosphorous oxychloride (11 mL, 0.12 mol) was dropped thereinto for 15 minutes. After stirring at 0° C. for 1 hour, cyclohexanone (5.5 mL, 0.053 mol) was added. After stirring at room temperature for 1 hour, heating to reflux was performed and stirring was further performed for 1 hour. After cooling to room temperature, 18 mL of a mixed solution of aniline/EtOH=1/1 (volume ratio) was added. After 30 minutes, 110 mL of a mixed solution of HExperimental Anhydrous DMF (13 mL, 0.17 mol) was placed in a 100 mL three-necked flask and cooled to 0°C. Phosphorous oxychloride (11 mL, 0.12 mol) was dropped thereinto for 15 minutes. Synthesis of Chloromalonaldehyde Dianil Chloride (Compound 18) 13 mL of anhydrous DMF are added under argon to a 250 mL flask fitted with a mechanical stirrer. 11 ml of POCl3, previously cooled to 4 C. in the refrigerator, are slowly added drop by drop. The reaction mixture is cooled to 0 C. with a NaCl/ice bath under continuous stirring. A solution of 2.65 mL of cyclohexanone in 5 mL of dichloromethane is added dropwise. The color of the reaction mixture turn to yellow. At the of the addition, the mixture is stirred for a further 15 minutes and then heated on a water bath for 1 hour. It is then cooled to room temperature and a cold solution of 10 mL of aniline in 10 mL of ethanol is added dropwise. The reaction mixture turn to deep violet and becomes very viscous. 100 mL of cold water and 10 mL of cold concentrated HCl are added. The reaction mixture is transferred to a beaker, covered and kept in a refrigerator at 4 C. overnight. A dark violet crystalline mass precipitates and is collected on a fritted glass filter and washed several times with cold water. The product is dried overnight in a desiccator. The UV-Vis absorption spectrum shows two peaks, at 520 and 415 nm.9, 10-dimethyl-3, 6-disulfoacridin-10-ium, triethylammonium salt (25 mg), and N-[(3-(Anilinomethylene)-2-chloro-1-cyclohexen-1-yl)methylene]aniline monohydrochloride (10 mg) are combined in 0.5 mL of acetic anhydride and 0.2 mL of acetic acid. Triethylamine (TEA) (0.02 mL) is added and the mixture is heated to 80 C. for 8 h. The crude product is precipitated with 5 mL of ethyl acetate, filtered and purified by HPLC to give the chloro-substituted acridinium dye.General procedure: (0268) The dyes, Table 14, were synthesized by condensation of the quaternary salt (Table 12) with the bridge (Table 13) in a mixture of acetic anhydride/acetic acid using cesium acetate as the base. [table-us-00017-en] TABLE 13 Bridge Intermediates B Intermediate B Structure B1 B2 B3 (0269) RRN 135, 137Symmetric Dyes (0270) To the mixture of the quaternary salt QS (48 mol), bridge B (20 mol), cesium acetate (480 mumol) was added 5 mL of a mixture of acetic anhydride/acetic acid (2:1, v/v). The mixture was heated at 40-50 C. for 4-8 h. After concentrating under vacuum to 1 mL, water (10 mL) was added and the mixture was purified using a packed C18 short column (12 mL bed volume), eluted with a gradient mixture of aqueous TEAA buffer and acetonitrile The volume was 20 mL each of the following TEAA/MeCN ratio (v/v): 95/5, 90/10, 85/15, 80/20, and 75/25. (0271) D81 was synthesized by condensation of QS1 with B3, LC/MS m/z=685.2 Da and 687.2 Da, M+1, UV-Vis lambdamax1026 nm (methanol).The compound 1-2 (941 mg, 2.67 mmol, 1 eq), the compound 1-3 (1 g, 2.67 mmol, 1 eq), the compound 1-4 (862 mg, 2.67 mmol, 1 eq) and sodium acetate (Sodium acetate, 438 mg, 5.34 mmol, 2 eq, Duksan) was added to 20 ml of ethanol and heated for 2 hours at 50 C. After completion of the reaction, the reaction mixture was cooled to room temperature, and the solvent was removed. The resulting solid particles were filtered, washed with ethyl acetate two or three times, and dried under reduced pressure to obtain Compound 1-5 (180 mg, 7.8%).-N, N-diethylamino-4-methy 1-flavylium tetrafluoroborate (10.6 mg, 0.028 mmol, 1.0 equiv.), N-[(3-(anilinomethylene)-2- chloro-1-cyclohexen-1-yl)methylene]aniline hydrochloride (4.5 mg, 0.013 mmol, 0.45 equiv.), and sodium acetate (6.9 mg, 0.084 mmol, 3.0 equiv.) were added to a flame -dried 1 mL vial and dissolved in 0.30 mL of a 7:3 mixture of -butanol:toluene. The mixture was freeze-pump- thawed x3 and heated to 100 C for 10 min. The crude product was purified by column chromatography in dichloromethane with a 0.5% to 6% ethanol solvent gradient to yield a purple solid (4.0 mg, 0.005 mmol 40 %). NMR (500 MHz, Acetonitnle-*) delta 8.04 (d, J= 13.8 Hz, 2H), 7.86 (d, J= 7.5 Hz, 4H), 7.62 (dd, J= 9.8, 3.7 Hz, 2H), 7.54 (dt, J= 26.9, 7.1 Hz, 6H), 7.18 (d, J= 3.6 Hz, 2H), 6.70 (dd, J= 13.8, 4.0 Hz, 2H), 6.66 - 6.59 (m, 2H), 6.40 (d, J = 2.1 Hz, 2H), 3.37 (t, J= 7.1 Hz, 8H), 2.74 (t, J= 6.0 Hz, 4H), {peak at 1.9-2.0 ppm, beneath CD3CN solvent peak, (m, 2H)}, 1.18 (t, J= 6.9 Hz, 12H). MS (ESI+): calculated for C48H48C1N202+[M]+: 719.3, found: 719.0. Absorbance (CH2C12): 524 nm (epsilon = 1.1 ± 0.1 x K^M' 1), 923 nm (epsilon = 4.4 ± 0.4 x 104M-1cm-1), 1034 nm (epsilon = 1.8 ± 0.2 x 10sM' 1). Emission (CH2C12, ex. 890 nm): 1062 nm.

Used as intermediate of telmisartan

Molecular Weight:359.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:358.1003540
Monoisotopic Mass:358.1003540
Topological Polar Surface Area:24.4
Heavy Atom Count:24
Complexity:466
Defined Bond Stereocenter Count:1
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes