5-methylhexanoic acid

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: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: The 5-methyl-caproic acid (30 g) was treated with methanol (600 ml) and sulfuric acid (3 ml), and thus methyl 5-methylcaproate was obtained. Yield : 27 g (81%).

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

Procedure: 4-(2-Fluoro-4-methanesulfonyl-phenoxy)-5-methyl-6-(piperidin-4-yloxy)-pyrimidine (42 mg, 0.1 mmol), 5-methyl-hexanoic acid (0.12 mmol, 1.2 eq), HATU (0.12 mmol, 1.2 eq), and triethylamine (0.2 mmol, 2 eq) were dissolved in DMF (1 mL), and then stirred at room temperature for 1 hour. The crude was filtered and then purified via prep-LCMS 5-95% to provide Compound C121 as a white powder (28.2 mg, 57%). Exact mass calculated for C24H32FN3O5S 493.2, found LCMS (ESI) m/z 494.5 (MH+). The crude was filtered purified via prep-LCMS 5-95%

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

Procedure: Working as in Example 1, but starting with 3-chloro-2-(7-chloro-1,8-naphthyridin-2yl)-1-isoindolinone (9.9 g) in anhydrous dimethylformamide (100 cc), 5-methylhexanoic acid (3.9 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (4.6 g), and after recrystallization in ethanol, 2-(7-chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 5-methylhexanoate (8 g), m.p. 132° C., is obtained. after recrystallization in ethanol

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

Procedure: The 5-methyl-caproic acid (30 g) was treated with methanol (600 ml) and sulfuric acid (3 ml), and thus methyl 5-methylcaproate was obtained. Yield: 27 g (81%).

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

Procedure: The 5-methyl-caproic acid (30 g) was treated with methanol (600 ml) and sulfuric acid (3 ml), and thus methyl 5-methylcaproate was obtained. Yield : 27 g (81%).

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

Procedure: The 5-methyl-caproic acid (30 g) was treated with methanol (600 ml) and sulfuric acid (3 ml), and thus methyl 5-methylcaproate was obtained. Yield : 27 g (81%).

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

Procedure: To a solution of dimethyl methylphosphonate (2.17 ml, 20 mmol) in anhydrous THF (20 mL), cooled at −78° C. was added n-BuLi (1.6 M in hexane, 13.7 mL, 22 mmol). The mixture was stirred for 30 minutes at this temperature under nitrogen. Methyl 5-methylhexanoate (1.44 g, 10 mmol), prepared from 5-methylhexanoic acid (from Avocado) and methanol at the presence of the catalytic amount of the concentrated sulfuric acid (the procedure described in Intermediate 17.1), was added dropwise for 10 minutes. The mixture was stirred for 2 hours at −78° C., gradually was warm to room temperature. The mixture was quenched with addition of 1N HCl to pH 4-5. The organic layer was separated, washed with brine and dried over MgSO4. The residue was purified through flash chromatography on silica gel (EtOAc:Hexanes=1:1) to give the product (1.80 g) with colorless oil in 76% yield. 1HNMR (CD3OD, ppm) δ 0.866 (d, J=6.5 Hz, 6H), 1.16 (m, 2H), 1.56 (m, 3H), 2.58 (t, J=7.3 Hz, 2H), 3.10 (d, J=22.7 Hz, 2H), 3.70 (s, 3H), 3.79 (s, 3H) was added dropwise for 10 minutes The mixture was stirred for 2 hours at −78° C. The mixture was quenched with addition of 1N HCl to pH 4-5 The organic layer was separated washed with brine dried over MgSO4 The residue was purified through flash chromatography on silica gel (EtOAc:Hexanes=1:1)