Di-tert-butylphenylphosphine

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:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a round bottomed flask containing 7-benzyl-2-chloro-4-phenyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine (73 mg, 0.22 mmol) was added commercially available 4-amino-N-(2,6-dimethylphenyl)benzamide (56 mg, 0.23 mmol), diacetoxypalladium (II), (12 mg, 0.05 mmol) di-tert-butyl(phenyl)phosphine (39 mg, 0.13 mmol), cesium carbonate (125 mg, 0.38 mmol), and toluene (5 mL). The reaction mixture was heated to 100° C. for 14 h, then cooled to rt and diluted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate, dried over sodium sulfate, filtered, and concentrated on a rotary evaporator. The material was purified by flash column chromatography to afford N-(2,6-dimethylphenyl)-4-{[4-phenyl-7-(phenylmethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl]amino}benzamide (60 mg, 50%) as an off white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.95 (s, 1H), 9.53 (s, 1H), 7.93 (m, 4H), 7.61 (m, 2H), 7.50 (m, 3H), 7.29 (m, 5H), 7.11 (m, 3H), 3.64 (m, 2H), 3.56 (m, 2H), 2.90 (m, 2H), 2.81 (m, 2H), 2.17 (s, 6H). MS (EI) for C35H33N5O: 540.3 (MH+). cooled to rt The organic layer was washed with saturated sodium bicarbonate dried over sodium sulfate filtered concentrated on a rotary evaporator The material was purified by flash column chromatography

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

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

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 183 mg (0.983 mmol) of 4-ethinyl-1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazole, 2.3 mg (0.01 mmol) of palladium acetate and 3.9 mg (0.02 mmol) of copper(I) iodide are weighed into a round-bottom flask and placed under protective gas. Subsequently, 9.1 mg (0.04 mmol) of di(tert-butyl)phenylphosphine, 300 mg (1.03 mmol) of 3,5-bis(trifluoromethyl)bromobenzene, 137 mg (1.08 mmol) of cyclohexyldimethylamine and dimethylacetamide (5 ml) are added and the mixture is heated to 110° C. for 12 h. After the end of the reaction, the mixture is cooled, poured onto cold, dilute hydrochloric acid and extracted with ether. The combined ether phases which have been dried over MgSO4 are concentrated. The product is obtained as a solid in an 85% yield. After the end of the reaction the mixture is cooled extracted with ether The combined ether phases which have been dried over MgSO4 are concentrated The product is obtained as a solid in an 85% yield

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 183 mg (0.983 mmol) of 4-ethinyl-1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazole, 2.3 mg (0.01 mmol) of palladium acetate and 3.9 mg (0.02 mmol) of copper(I) iodide are weighed into a round-bottom flask and placed under protective gas. Subsequently, 9.1 mg (0.04 mmol) of di(tert-butyl)phenylphosphine, 300 mg (1.03 mmol) of 3,5-bis(trifluoromethyl)bromobenzene, 137 mg (1.08 mmol) of cyclohexyldimethylamine and dimethylacetamide (5 ml) are added and the mixture is heated to 110° C. for 12 h. After the end of the reaction, the mixture is cooled, poured onto cold, dilute hydrochloric acid and extracted with ether. The combined ether phases which have been dried over MgSO4 are concentrated. The product is obtained as a solid in an 85% yield. After the end of the reaction the mixture is cooled extracted with ether The combined ether phases which have been dried over MgSO4 are concentrated The product is obtained as a solid in an 85% yield

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2.00 g (8.23 mmol) of 4-bromo-1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazole, 18.5 mg (0.08 mmol) of palladium acetate and 60.3 mg (0.165 mmol) of tetra-n-butylammonium bromide are weighed into the glass insert of an autoclave together with 73.2 mg (0.329 mmol) of di(tert-butyl)phenylphosphine, 1.77 g (9.05 mmol) of dicyclohexylmethylamine, 9.1 mg (0.082 mmol) of hydroquinone and dimethylacetamide (22.8 ml), and placed under a protective gas atmosphere. Subsequently, 2.57 g (41.2 mmol) of vinyl chloride are metered in at 20° C. and the reaction mixture is stirred at 130° C. for 30 h. After the end of the reaction, the mixture is cooled, poured onto cold, dilute hydrochloric acid and extracted with CH2C12. The combined organic phases which have been dried over magnesium sulphate are concentrated. The product is obtained as a solid in a 69% yield. are metered in at 20° C. After the end of the reaction the mixture is cooled extracted with CH2C12 The combined organic phases which have been dried over magnesium sulphate are concentrated The product is obtained as a solid in a 69% yield

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10.0 g (41.2 mmol) of 4-bromo-1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazole, 92.4 mg (0.41 mmol) of palladium acetate and 302 mg (0.82 mmol) of tetra-n-butylammonium bromide are weighed into the glass insert of an autoclave together with 366 mg (1.65 mmol) of di(tert-butyl)phenylphosphine, 8.84 g (45.3 mmol) of dicyclohexylmethylamine and dimethylacetamide (34.3 ml), and placed under a protective gas atmosphere. Subsequently, 30 bar of ethylene are injected at 20° C. and the reaction mixture is stirred at 130° C. for 30 h. After the end of the reaction, the mixture is cooled, poured onto cold dilute hydrochloric acid and extracted with CH2C12. The combined organic phases which have been dried over magnesium sulphate are concentrated. The product is obtained as a brown oil in an 83% yield. are injected at 20° C. After the end of the reaction the mixture is cooled extracted with CH2C12 The combined organic phases which have been dried over magnesium sulphate are concentrated The product is obtained as a brown oil in an 83% yield