1-(2,6-dichlorophenyl)ethanol

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

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

Procedure: 3-Bromo-6-nitrofuro[3,2-c]pyridin-7-ol (Intermediate 10) was reacted with racemic 1-(2,6-dichlorophenyl)ethanol following the procedure described for Intermediate 8. The resulting 3-Bromo-7-[1-(2,6-dichlorophenyl)ethoxy]-6-nitrofuro[3,2-c]pyridine was reacted with iron/HCl as described in Example 2 to give 3-Bromo-7-[1-(2,6-dichlorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine. Suzuki coupling with 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl ester and Boc removal with HCl as described for Example 333 gave the title compound as HCl salt. 1H NMR (400 MHz, CD3OD): δ=1.86 (d, J=6.8 Hz, 3H), 1.91-2.03 (m, 2H), 2.11 (dd, J=12.0, 2.2 Hz, 2H), 2.75 (td, J=12.8, 2.5 Hz, 2H), 3.13-3.23 (m, 2H), 4.26-4.39 (m, 1H), 6.59 (q, J=6.8 Hz, 1H), 7.23 (d, J=7.8 Hz, 1H), 7.31-7.39 (m, 2H), 7.77 (s, 1H), 7.82 (s, 1H), 8.07 (s, 1H), 8.13 (s, 1H). MS (ES+): m/z 472.00/474.00 [MH+]. HPLC: tR=2.38 min (ZQ3, polar—5 min).

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

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

Procedure: a solution of 5 g of 2,4,6-trichloro-1,3,5-triazine in 5.5 cm3 of N,N-dimethylformamide is stirred for about 3 hours at a temperature close to 20° C. A white precipitate forms. A solution of 5 g of 1-(2,6-dichlorophenyl)-ethanol in 72 cm3 of dichloromethane is added dropwise without exceeding 25° C. After about 48 hours at a temperature close to 20° C., the suspension is solubilized by adding 150 cm3 of dichloromethane. The solution obtained is washed five times with 40 cm3 of water, then dried over magnesium sulphate, filtered and concentrated under reduced pressure. After filtration of the residue on 100 cm3 of silica [eluent: cyclohexane/ethyl acetate (75/25 by volume)], we obtain 5.5 g of 1,3-dichloro-2-(1-chloroethyl)benzene in the form of a colorless oil, which has the following characteristics: close to 20° C without exceeding 25° C After about 48 hours at a temperature close to 20° C. The solution obtained is washed five times with 40 cm3 of water dried over magnesium sulphate filtered concentrated under reduced pressure After filtration of the residue on 100 cm3 of silica [eluent: cyclohexane/ethyl acetate (75/25 by volume)], we

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

Procedure: 3-Bromo-6-nitrofuro[3,2-c]pyridin-7-ol (Intermediate 10) was reacted with racemic 1-(2,6-dichlorophenyl)ethanol following the procedure described for Intermediate 8. The resulting 3-Bromo-7-[1-(2,6-dichlorophenyl)ethoxy]-6-nitrofuro[3,2-c]pyridine was reacted with iron/HCl as described in Example 2 to give 3-Bromo-7-[1-(2,6-dichlorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine. Suzuki coupling with 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl ester and Boc removal with HCl as described for Example 333 gave the title compound as HCl salt. 1H NMR (400 MHz, CD3OD): δ=1.86 (d, J=6.8 Hz, 3H), 1.91-2.03 (m, 2H), 2.11 (dd, J=12.0, 2.2 Hz, 2H), 2.75 (td, J=12.8, 2.5 Hz, 2H), 3.13-3.23 (m, 2H), 4.26-4.39 (m, 1H), 6.59 (q, J=6.8 Hz, 1H), 7.23 (d, J=7.8 Hz, 1H), 7.31-7.39 (m, 2H), 7.77 (s, 1H), 7.82 (s, 1H), 8.07 (s, 1H), 8.13 (s, 1H). MS (ES+): m/z 472.00/474.00 [MH+]. HPLC: tR=2.38 min (ZQ3, polar—5 min).