N-benzylpropan-2-amine

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:

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

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

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a microwave tube was added 1 eq. of 4-(2-chlorophenyl)-2-morpholino pyrimidine-5-carboxylic acid (80 mg), 1.1 eq. of isopropyl benzylamine (43 mL), 2.5 eq. of triethylamine (80 mL) and 1.2 eq. of BtSO2Me in 4 mL of dioxane. The reaction mixture was heated to 160° C./300 W for 1200 sec. The crude product was purified by prep HPLC. ES+=451.0. NMR confirmed the structure. The crude product was purified by prep HPLC

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

Procedure: A solution of 2 M oxalyl chloride in CH2Cl2 (0.070 mL, 0.14 mmol) was added to a stirred solution of 4-(2-fluorophenyl)-6-methyl-2-morpholin-4-yl-pyrimidine-5-carboxylic acid (0.03 g, 0.09 mmol) in CH2Cl2 (2 mL) and DMF (0.030 mL) at room temperature, and stirring continued for 15 min. A solution of N-benzylisopropylamine (0.013 g, 0.1 mmol) in CH2Cl2(1 mL) and diisopropylethylamine (0.044 mL, 0.25 mmol) were added and stirred for 24 hr. The solvent was removed under reduced pressure, and the residue was purified by Biotage SP1 on packed silica gel column (10%-80% EtOAc/Hexanes gradient) to give 4-(2-fluorophenyl)-6-methyl-2-morpholin-4-yl-pyrimidine-5-carboxylic acid benzyl-isopropyl-amide (0.016 g, 40%). Mass Spec. LCMS 449(M+1). stirred for 24 hr The solvent was removed under reduced pressure the residue was purified by Biotage SP1

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ice-cooled solution of 4-(2-fluoro-phenyl)-2-morpholin-4-yl-pyrimidine-5-carboxylic acid (4.321 g, 14.25 mmol) in CH2Cl2 (100 mL) and DMF (2 drops) was added oxalyl chloride (1.5 mL, 2.21 g, 17.5 mmol) dropwise. Most solids dissolved at first, later a precipitate formed. The suspension was stirred for 1 hour at 0° C., and then allowed to warm to room temperature (all solids dissolved). The solution was concentrated to a dark oil, which crystallized upon standing. The crude acid chloride was taken up in toluene (50 mL, distilled, dried over Na2SO4) and cooled in ice. N-Isopropylbenzylamine (9.5 mL, 8.5 g, 56.8 mmol) was added. The resulting suspension was stirred at room temperature for 90 minutes, washed with water and a saturated aqueous NaCl solution, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (400 mL silica, EtOAc/heptanes 1:1). All fractions containing the product were combined and concentrated. Some of the excess amine eluted with the product. A solution of the mixture in CH2Cl2 (50 mL) was washed with a 10% aqueous citric acid solution (2×25 mL), water (25 mL), and saturated aqueous NaCl solution (25 mL), dried over Na2SO4, and concentrated to give pure 4-(2-fluoro-phenyl)-2-morpholin-4-yl-pyrimidine-5-carboxylic acid benzyl-isopropyl-amide as a yellowish foam (5.685 g, 13.08 mmol, 92%). Most solids dissolved at first, later a precipitate formed to warm to room temperature (all solids dissolved) The solution was concentrated to a dark oil, which crystallized cooled in ice The resulting suspension was stirred at room temperature for 90 minutes washed with water a saturated aqueous NaCl solution, dried over Na2SO4 concentrated The crude product was purified by column chromatography (400 mL silica, EtOAc/heptanes 1:1) All fractions containing the product concentrated Some of the excess amine eluted with the product A solution of the mixture in CH2Cl2 (50 mL) was washed with a 10% aqueous citric acid solution (2×25 mL), water (25 mL), and saturated aqueous NaCl solution (25 mL) dried over Na2SO4 concentrated

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6 (200 mg, 0.87 mmol), N-benzylpropan-2-amine (0.58 mL, 3.47 mmol), Pd(OAc)2 (8 mg, 0.03 mmol), X-Phos (33 mg, 0.07 mmol), and NaOtBu (250 mg, 2.6 mmol) were suspended in dioxane (3 mL), and stirred for 5 minutes at 150° C. via microwave. The reaction solution was diluted with DMSO and filtered. The crude product was purified directly via prep-LC-MS to provide 448 (21 mg, 7% yield) as a white powder. LC-MS (M+H=344, obsd.=344). 1H NMR (400 MHz, DMSO-D6) δ 11.45 (m, 1H), 8.53 (m, 1H), 8.38 (m, 1H), 8.00 (s, 1H), 7.49 (m, 1H), 7.32 (m, 5H), 7.18 (m, 1H), 7.00 (m, 1H), 4.66 (s, 2H), 1.25 (d, J=6.6, 6H), 0.84 (m, 1H). filtered The crude product was purified directly via prep-LC-MS