2-methylbenzamide

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: To a solution of o-toluamide (13.5 g, 0.100 mol) in dichloromethane (150 mL) was added a solution (1.0 M, 106 mL, 0.106 mol) of triethyloxonium tetrafluoroborate in dichloromethane. The resulting mixture was stirred at room temperature for 14 h. Two-thirds of dichloromethane was evaporated under reduced pressure. After addition of ether (400 mL) to the concentrate, the mixture was stirred for 3 h under ice-cooling. Precipitates were collected by filtration, washed with ether, and dried in vacuo to give 21.7 g (86%) of ethyl 2-methylbenzimidate hydrotetrafluoroborate as a colorless solid. Two-thirds of dichloromethane was evaporated under reduced pressure After addition of ether (400 mL) to the concentrate the mixture was stirred for 3 h under ice- cooling Precipitates were collected by filtration washed with ether dried in vacuo

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

Procedure: 2,2,2-Trichloro-1,1-ethanediol and o-toluamide were processed as described in Example 37C to provide the desired product.

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

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Treat the product of step 5 (10.54 g, 23.3 mmol) in THF (170 mL) with 60% NaH (1.87 g, 47 mmol) followed by CH31I (1.9 mL, 30.5 mmol). Heat the reaction mixture at 60° C. for 30 min and then partition between Et2O (250 mL) and H2O (500 mL). Extract the aqueous layer with Et2O (500 mL), wash the combined organic layers with brine (250 mL), dry with MgSO4 and concentrate to give 9.9 g of the methyl benzamide product as a colorless oil (21 mmol, 91%). partition between Et2O (250 mL) and H2O (500 mL) Extract the aqueous layer with Et2O (500 mL) wash the combined organic layers with brine (250 mL) dry with MgSO4 concentrate

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

Procedure: Formula I where R2 and R3 are H; R5 is Benzyl; R6 is Isopropyl; R6′ is H; R7 is 3-Amino-propyl-; R8 is —C(O)—R9 where R9 is p-Methyl-phenyl-; X and Y are —C═; and W and Z are —N═: The toluamide, {3-[[1-(3-benzyl-4-oxo-3,4-dihydro-pteridin-2-yl)-2-methyl-propyl]-(4-methyl-benzoyl)-amino]-propyl}-carbamic acid tert-butyl ester, was then dissolved in TFA/H2O (95/5) (50 mL) and stirred at room temperature for 1 hour, after which it was diluted with dichloromethane, washed with saturated sodium bicarbonate, water and brine, and dried over sodium sulfate. Concentration of the dichloromethane solution gave the title product (±)-N-(3-amino-propyl)-N-[1-(3-benzyl-4-oxo-3,4-dihydro-pteridin-2-yl)-2-methyl-propyl]4-methyl-benzamide as a white solid (150 mg, 98.0%). MS (Cl) M/E: 485.2. washed with saturated sodium bicarbonate, water and brine dried over sodium sulfate

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

Procedure: A mixture containing 48 g (0.36 mole) of 2-methylbenzamide, 74 g (0.36 mole) of phosphorus pentachloride and 500 ml of AR carbon tetrachloride was heated at 60°-70° for 30 min. at which time the HCl gas evolution had ceased. The solution was cooled to 30° and 16.9 g (0.36 mole) of 97% formic acid added dropwise. Stirring was continued following the addition for 40-50 min. The product was colleted, washed with AR carbon tetrachloride and air-dried to give 56 g, m.p. 91°-93°. The solution was cooled to 30° the addition for 40-50 min washed with AR carbon tetrachloride air-dried to give 56 g, m.p. 91°-93°

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

Procedure: Formula I where R2 and R3 are H; R5 is Benzyl; R6 is Isopropyl; R6′ is H; R7 is 3-Amino-propyl-; R8 is —C(O)—R9 where R9 is p-Methyl-phenyl-; X and Y are —C═; and W and Z are —N═: The toluamide, {3-[[1-(3-benzyl-4-oxo-3,4-dihydro-pteridin-2-yl)-2-methyl-propyl]-(4-methyl-benzoyl)-amino]-propyl}-carbamic acid tert-butyl ester, was then dissolved in TFA/H2O (95/5) (50 mL) and stirred at room temperature for 1 hour, after which it was diluted with dichloromethane, washed with saturated sodium bicarbonate, water and brine, and dried over sodium sulfate. Concentration of the dichloromethane solution gave the title product (±)-N-(3-amino-propyl)-N-[1-(3-benzyl-4-oxo-3,4-dihydro-pteridin-2-yl)-2-methyl-propyl]-4-methyl-benzamide as a white solid (150 mg, 98.0%). MS (Cl) M/E: 485.2. washed with saturated sodium bicarbonate, water and brine dried over sodium sulfate