[(2S)-piperidin-2-yl]methanol

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

Procedure: At 0° C. 86 mg (0.44 mmol) (2S)-piperidin-2-ylmethanol were added to 132 mg (3.3 mmol) sodium hydride (60% in mineral oil) in 4 mL anhydrous THF. After 15 min of stirring on the ice bath, 141 mg (0.33 mmol) of 6-chloro-3-(4-methoxyfuro[3,2-c]-pyridin-2-yl)imidazo[1,2-b]pyridazine were added. The ice bath was removed and the mixture was stirred for 72 h at 40° C. At 0° C were added The ice bath was removed

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

Procedure: Following the procedure for 103, 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (50.0 mg, 0.2 mmol) was reacted with (S)-piperidin-2ylmethanol (1.2 equiv) to give 162 (12.1 mg, M+1 411.1)

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

Procedure: Following the procedure for 103, 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (50.0 mg, 0.2 mmol) was reacted with (S)-piperidin-2ylmethanol (1.2 equiv) to give 162 (12.1 mg, M+1 411.1)

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

Procedure: (S)-Piperidin-2-ylmethanol (1.1 eq.) was dissolved in dichloromethane (4 ml/mmol) and cooled, and triethylamine (2.5 eq.) was added. A solution of 4-methoxy-2,6-dimethylbenzenesulfonyl chloride (1 eq.) in dichloromethane (2 ml/mmol) was added dropwise at 0° C., and then stirring was carried out for 90 min at room temperature. Hydrogen chloride solution (eq., 0.5 mol/l, 2 ml/mmol) was added, stirring was carried out for 15 min, and the phases were separated. The organic phase was washed with water, dried over sodium sulfate and concentrated in vacuo. The crude product was used in the next stage without being purified further. Yield: 20% cooled stirring was carried out for 15 min the phases were separated The organic phase was washed with water dried over sodium sulfate concentrated in vacuo without being purified further

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

Procedure: (S)-Piperidin-2-ylmethanol (1.1 eq.) was dissolved in dichloromethane (4 ml/mmol) and cooled, and triethylamine (2.5 eq.) was added. A solution of 4-methoxy-2,6-dimethylbenzenesulfonyl chloride (1 eq.) in dichloromethane (2 ml/mmol) was added dropwise at 0° C., and then stirring was carried out for 90 min at room temperature. Hydrogen chloride solution (eq., 0.5 mol/l, 2 ml/mmol) was added, stirring was carried out for 15 min, and the phases were separated. The organic phase was washed with water, dried over sodium sulfate and concentrated in vacuo. The crude product was used in the next stage without being purified further. Yield: 20% cooled stirring was carried out for 15 min the phases were separated The organic phase was washed with water dried over sodium sulfate concentrated in vacuo without being purified further

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

Procedure: Following the procedure for 103, 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (50.0 mg, 0.2 mmol) was reacted with (S)-piperidin-2-ylmethanol (1.2 equiv) to give 162 (12.1 mg, M+1 411.1)

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

Procedure: Following the procedure for 103, 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (50.0 mg, 0.2 mmol) was reacted with (S)-piperidin-2-ylmethanol (1.2 equiv) to give 162 (12.1 mg, M+1 411.1)

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

Procedure: At 0° C. 86 mg (0.44 mmol) (2S)-piperidin-2-ylmethanol were added to 132 mg (3.3 mmol) sodium hydride (60% in mineral oil) in 4 mL anhydrous THF. After 15 min of stirring on the ice bath, 141 mg (0.33 mmol) of 6-chloro-3-(4-methoxyfuro[3,2-c]-pyridin-2-yl)imidazo[1,2-b]pyridazine were added. The ice bath was removed and the mixture was stirred for 72 h at 40° C. At 0° C were added The ice bath was removed

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

Procedure: Following the procedure for 103, 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (50.0 mg, 0.2 mmol) was reacted with (S)-piperidin-2ylmethanol (1.2 equiv) to give 162 (12.1 mg, M+1 411.1)

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

Procedure: At 0° C. 86 mg (0.44 mmol) (2S)-piperidin-2-ylmethanol were added to 132 mg (3.3 mmol) sodium hydride (60% in mineral oil) in 4 mL anhydrous THF. After 15 min of stirring on the ice bath, 141 mg (0.33 mmol) of 6-chloro-3-(4-methoxyfuro[3,2-c]-pyridin-2-yl)imidazo[1,2-b]pyridazine were added. The ice bath was removed and the mixture was stirred for 72 h at 40° C. At 0° C were added The ice bath was removed

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

Procedure: Following the procedure for 103, 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (50.0 mg, 0.2 mmol) was reacted with (S)-piperidin-2ylmethanol (1.2 equiv) to give 162 (12.1 mg, M+1 411.1)