5-bromo-1-chloro-2,3-dihydro-1H-indene

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

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

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-1-chloro-indane (542 mg, 2.35 mmol) in toluene (9 ml) was added dimethylamine (3 ml) and resulting mixture was heated at 90° C. for 1.5 hr. The reaction mixture is concentrated under reduced pressure to yield the title compound (300 mg, 53%). 1H NMR (CDCl3): 2.06 (m, 2H), 2.24 (s, 6H), 2.81-2.93 (m, 2H), 4.27 (t, 1H), 7.22 (d, 1H), 7.33 (d 1H), 7.36 (s, 1H). resulting mixture The reaction mixture is concentrated under reduced pressure

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

Procedure: 3.09 mL (37.45 mmol) of thionyl chloride, dissolved in cooled dichloromethane, are added dropwise at −10° C. to a solution of 3.8 g (17.83 mmol) of 5-bromoindan-1-ol in 200 mL dichloromethane. The reaction mixture is allowed to come up slowly to ambient temperature and stirred for 14 hours at ambient temperature. Then ice and 100 mL of dilute sodium hydrogen carbonate solution are added successively. The organic phase is extracted twice with 50 mL of water. The combined organic phases are dried over magnesium sulfate, filtered and the solvent is distilled off. Yield: 3.7 g (90% of theory); C9H8BrCl (M=231.52); Rf value: 0.91 (silica gel, petroleum ether/ethyl acetate (6:4)). to come up slowly to ambient temperature The organic phase is extracted twice with 50 mL of water The combined organic phases are dried over magnesium sulfate filtered the solvent is distilled off

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 47.3 (0.16 mmol) and methyl 3-(4-hydroxyphenyl)-3-(1H-pyrazol-1-yl)propanoate 47.4 (obtained by the procedure of Example 58 set forth in US 2006/0004012 which is hereby incorporated by reference) (0.11 mmol) was stirred at 40° C. for 1 hour. After work up and chromatography, 47.5 was obtained in 30% yield. MS ESI (pos.) M/E: 441, 443 (M+H). obtained by the procedure of Example 58 After work up and chromatography, 47.5 was obtained in 30% yield

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 47.3 (0.16 mmol) and methyl 3-(4-hydroxyphenyl)-3-(1H-pyrazol-1-yl)propanoate 47.4 (obtained by the procedure of Example 58 set forth in US 2006/0004012 which is hereby incorporated by reference) (0.11 mmol) was stirred at 40° C. for 1 hour. After work up and chromatography, 47.5 was obtained in 30% yield. MS ESI (pos.) M/E: 441, 443 (M+H). obtained by the procedure of Example 58 After work up and chromatography, 47.5 was obtained in 30% yield

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

Procedure: A mixture of 47.2 (11.1 mmol) and thionyl chloride (44 mmol) in DCM (20 mL) was stirred at room temperature overnight. After evaporation of solvent, 47.3 was obtained and it was used without further purification. After evaporation of solvent 47.3 was obtained it was used without further purification

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

Procedure: A solution of 1.1 (2.0 g) in DCM (10 mL) in an ice-bath, was treated with thionyl chloride (10 mL). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured into ice water and extracted with EtOAc. The organic layer was dried (MgSO4), filtered, and concentrated under vacuum. The resulting material was chromatographed on a silica gel column, eluting with 5-10% EtOAc in hexane, to afford 1.2. 1H NMR (DMSO-d6) δ 7.54 (s, 1H), 7.45 (dd, 1H, J1=1.0 Hz, J2=8.50 Hz), 7.37 (d, 1H, J=8.0 Hz), 3.07 (m, 1H), 5.60 (q, 1H), 2.93 (m, 1H), 2.59 (m, 1H), 2.26 (m, 1H). extracted with EtOAc The organic layer was dried (MgSO4) filtered concentrated under vacuum The resulting material was chromatographed on a silica gel column eluting with 5-10% EtOAc in hexane to afford 1.2

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

Procedure: A solution of 1.1 (2.0 g) in DCM (10 mL) in an ice-bath, was treated with thionyl chloride (10 mL). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured into ice water and extracted with EtOAc. The organic layer was dried (MgSO4), filtered, and concentrated under vacuum. The resulting material was chromatographed on a silica gel column, eluting with 5-10% EtOAc in hexane, to afford 1.2. 1H NMR (DMSO-d6) δ 7.54 (s, 1H), 7.45 (dd, 1H, J1=1.0 Hz, J2=8.50 Hz), 7.37 (d, 1H, J=8.0 Hz), 3.07 (m, 1H), 5.60 (q, 1H), 2.93 (m, 1H), 2.59 (m, 1H), 2.26 (m, 1H). extracted with EtOAc The organic layer was dried (MgSO4) filtered concentrated under vacuum The resulting material was chromatographed on a silica gel column eluting with 5-10% EtOAc in hexane to afford 1.2

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

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