1-isothiocyanato-2-methoxybenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound of example 280 was prepared analogous to compound of example 256 by reaction of compound of example 223 with 2-methoxyphenyl isothiocyanate. The compound of example 280 was used directly without isolation, for the preparation of compound of example 281.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound of example 73 was prepared analogous to compound of example 51 by reaction of compound of example 6 with 2-methoxyphenyl isothiocyanate. The compound of example 73 was used directly without isolation for the preparation of compound of example 74.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Isothiocyanato-2-methoxy-benzene (0.76 mL, 5.45 mmol) was added to a solution of 2-amino-4-methyl-benzoic acid methyl ester (900 mg, 5.45 mmol) and acetic acid (1.5 mL) in ethanol (10 mL), and heated at reflux for 16 hr. The reaction mixture was cooled to room temperature and diluted with ethanol. The precipitated solid was filtered, washed with ethanol and dried to afford 2-mercapto-3-(2-methoxy-phenyl)-7-methyl-3H-quinazolin-4-one (1.0 g, 62%) as white solid. heated at reflux for 16 hr The precipitated solid was filtered washed with ethanol dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Isothiocyanato-2-methoxy-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(2-methoxy-phenyl)-amine as brown solid in 33% yield. was then heated at the reflux temperature for 24 hr extracted with ethyl acetate The target product was purified by gravity column chromatography (50% EtOAc in hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(3-Bromo-pyridin-2-yl)-3-(2-methoxy-phenyl)-thiourea was prepared from 3-bromo-pyridin-2-ylamine (5.0 g, 29.0 mmol) and 1-isothiocyanato-2-methoxy-benzene (4.0 mL, 29.0 mmol) in a manner analogous to Step 19a. The reaction product was isolated as a yellow solid (8.46 g, 86%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 13.62 (br s, 1H), 8.75-8.65 (m, 2H), 8.21 (dd, J=5.1, 1.5 Hz, 1H), 7.91 (dd, J=8.0, 1.6, Hz, 1H), 7.21 (dt, J=7.9, 1.5 Hz, 1H), 7.06-7.00 (m, 1H), 6.98-6.94 (m, 1H), 6.91 (dd, J=7.9, 5.0 Hz, 1H), 3.93 (s, 3H). MS=340 (MH)+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Pipemidic acid (53 mg, 0.175 mmol) and 2-methoxyphenyl isothiocyanate (20 μL, 0.145 mmol) were used. Purification on silica yielded compound 21 in Table 1, below (36 mg, 53%). 1H NMR (250 MHz, CDCl3) δ 9.33 (s, 1H), 8.68 (s, 1H), 7.84 (d, J=7.30 Hz, 1H), 7.54 (s, 1H), 7.20-7.04 (m, 1H), 7.03-6.85 (m, 2H), 4.44-3.73 (m, 13H), 1.49 (t, J=6.60 Hz, 3H) ppm. Purification on silica yielded compound 21 in Table 1

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Pipemidic acid (53 mg, 0.175 mmol) and 2-methoxyphenyl isothiocyanate (20 μL, 0.145 mmol) were used. Purification on silica yielded compound 21 in Table 1, below (36 mg, 53%). 1H NMR (250 MHz, CDCl3) δ 9.33 (s, 1H), 8.68 (s, 1H), 7.84 (d, J=7.30 Hz, 1H), 7.54 (s, 1H), 7.20-7.04 (m, 1H), 7.03-6.85 (m, 2H), 4.44-3.73 (m, 13H), 1.49 (t, J=6.60 Hz, 3H) ppm. Purification on silica yielded compound 21 in Table 1

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound of example 280 was prepared analogous to compound of example 256 by reaction of compound of example 223 with 2-methoxyphenyl isothiocyanate. The compound of example 280 was used directly without isolation, for the preparation of compound of example 281.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound of example 73 was prepared analogous to compound of example 51 by reaction of compound of example 6 with 2-methoxyphenyl isothiocyanate. The compound of example 73 was used directly without isolation for the preparation of compound of example 74.

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 mg of 11-amino-2-[2-(dimethylamino)ethyl]-1H-dibenzo[de,h]isoquinoline-1,3(2H)-dione (obtained in example 3) (0.30 mmole) were dissolved in 8 ml of acetonitrile. 83 μl (2 molar equivalents) of 2-methoxyphenyl isothiocyanate was added and the reaction mixture was maintained at room temperature for 45 hours at 55° C. The solvent was then evaporated under reduced pressure and the residue was submitted to a flash chromatography (SiO2, CH2Cl2/MeOH 95/5). 142 mg of the desired product (formula shown hereinabove) were isolated as a red powder (yield=95%) which was characterized as follows: The solvent was then evaporated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir: