4-propan-2-ylcyclohexan-1-one

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

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

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

Procedure: To a solution of hydroxylamine-O-sulfonic acid (60.5 g, 535 mmol) in formic acid (320 ml) was added dropwise a solution of 4-isopropyl cyclohexanone (50.0 g, 357 mmol) in formic acid (110 ml) at r.t. under an argon atmosphere. The reaction mixture was refluxed for 3 h, cooled to r.t. and slowly treated with ice-water (550 ml). 10 N NaOH (1.1 liter) was added to adjust the pH to 8 and the resultant mixture was extracted with CHCl3 (4×). The combined organic extracts were washed with water, brine, dried (MgSO4), filtered and concentrated under reduced pressure. The light-brown solid was crystallized from n-heptane: 42.4 g (75%); The reaction mixture was refluxed for 3 h the resultant mixture was extracted with CHCl3 (4×) The combined organic extracts were washed with water, brine dried (MgSO4) filtered concentrated under reduced pressure The light-brown solid was crystallized from n-heptane

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

Procedure: To a solution of hydroxylamine-O-sulfonic acid (60.5 g, 535 mmol) in formic acid (320 ml) was added dropwise a solution of 4-isopropyl cyclohexanone (50.0 g, 357 mmol) in formic acid (110 ml) at r.t. under an argon atmosphere. The reaction mixture was refluxed for 3 h, cooled to r.t. and slowly treated with ice-water (550 ml). 10 N NaOH (1.1 liter) was added to adjust the pH to 8 and the resultant mixture was extracted with CHCl3 (4×). The combined organic extracts were washed with water, brine, dried (MgSO4), filtered and concentrated under reduced pressure. The light-brown solid was crystallized from n-heptane: 42.4 g (75%); The reaction mixture was refluxed for 3 h the resultant mixture was extracted with CHCl3 (4×) The combined organic extracts were washed with water, brine dried (MgSO4) filtered concentrated under reduced pressure The light-brown solid was crystallized from n-heptane

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

Procedure: Using the procedure outlined in Example 1, 4-isopropylcyclohexanone and benzylamine were converted to the title compound: RT=2.52 min; m/z (ES+)=232.1 [M+H]+.

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

Procedure: The title compound was prepared as a white solid from reaction of N-azetidin-3-yl-2-(1-benzyl-5-trifluoromethyl-1H-indazol-3-ylamino)-acetamide and 4-isopropyl-cyclohexanone using the procedure described in Step E of Example 1.

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

Procedure: The title compound was prepared as a white solid from reaction of 3-[(azetidin-3-ylcarbamoylmethyl)-amino]-5-trifluoromethyl-indazole-1-carboxylic acid isopropylamide (as prepared in Example 90, Step A) and 4-iso-propyl-cyclohexanone using the procedure described in Step E of Example 1.

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

Procedure: The title compound was prepared as a white solid from reaction of N-azetidin-3-yl-2-(1-ethyl-5-trifluoromethyl-1H-indazol-3-ylamino)-acetamide TFA salt (as prepared in Example 67, Step A) and 4-isopropyl-cyclohexanone using the procedure described in Step E of Example 1.

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

Procedure: The title compound was prepared as a white solid from reaction of N-azetidin-3-yl-2-(5-trifluoromethyl-1H-indazol-3-ylamino)-acetamide (as prepared in Example 41, Step A) and 4-isopropyl-cyclohexanone using the procedure described in Step E of Example 1.

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

Procedure: The title compound was prepared as a white solid from reaction of N-azetidin-3-yl-2-(5-trifluoromethoxy-benzo[d]isoxazol-3-ylamino)-acetamide TFA salt (as prepared in Example 1, Step D) and 4-isopropyl-cyclohexanone using the procedure described in Step E of Example 1.

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

Procedure: The title compound was prepared as a white solid from reaction of (N-Azetidin-3-yl-2-(5-trifluoromethyl-benzo[d]isoxazol-3-ylamino)-acetamide TFA salt (as prepared in Example 1, Step D) and 4-isopropyl-cyclohexanone using the procedure described in Step E of Example 1.

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

Procedure: To a solution of 4-isopropylcyclohexanone (5.0 g, 36 mmol) and benzylamine (3.54 mL, 32 mmol) in MeOH (40 mL) was added 4 Å molecular sieves (2 g). After 16 h at rt NaBH4 (2.45 g, 65 mmol) was added and the mixture stirred for a further 6 h. Water (3 mL) was added and the solvent was removed in vacuo. The residue was partitioned between NaHCO3 (150 mL) and EtOAc (150 mL), the aqueous layer was extracted with EtOAc (2×50 mL) and the combined organic phases were washed with brine (2×50 mL) and dried (MgSO4). Solvent was removed in vacuo and the residue purified by column chromatography (SiO2, NH4OH:MeOH:DCM 0.25:5:95) to give the product as a free base. 4M HCl in dioxane and Et2O were added to the residue, and the resulting precipitate was filtered to give the title compound: δH (CD3OD) 0.92-0.97 (6H, m), 1.17-1.26 (1H, m), 1.53-1.92 (9H, m), 3.21-3.29 (1H, m), 4.23 (2H, s) 7.44-7.54 (5H, m). the solvent was removed in vacuo The residue was partitioned between NaHCO3 (150 mL) and EtOAc (150 mL) the aqueous layer was extracted with EtOAc (2×50 mL) the combined organic phases were washed with brine (2×50 mL) dried (MgSO4) Solvent was removed in vacuo the residue purified by column chromatography (SiO2, NH4OH:MeOH:DCM 0.25:5:95) to give the product as a free base the resulting precipitate was filtered