Reaction #2146775

Reaction equation

(1S)-1-phenylethanamine

(1S)-1-phenylethanamine

2-Chloro-9-cyclopentyl-5,7,7-trimethyl-8,9-dihydro-5H-pyrimido[5,4-b][1,4]diazepin-6(7H)-one

DIPEA

→

title compound

Yield 26.3%

(S)-9-cyclopentyl-5,7,7-trimethyl-2-(1-phenylethylamino)-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one

Yield 26.3%

Solvents

butyl alcohol

n-butyl alcohol

Conditions

Workup

1. 1
   Temperaturethe reaction mixture heated for 90 minutes in microwave at 140° C
2. 2
   OtherThe solvent was removed in vacuo
3. 3
   workup.DISSOLUTIONthe residue dissolved in dichloromethane
4. 4
   Washwashed sequentially with 0.5M HCl (three times, 5 mL each), saturated aqueous sodium hydrogen carbonate solution (three times, 5 mL each), and brine (once, 5 mL)
5. 5
   DryingThe washed solution was dried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated in vacuo
8. 8
   Otherto give yellow oil
9. 9
   OtherThe oil was purified by mass

Procedure

2-Chloro-9-cyclopentyl-5,7,7-trimethyl-8,9-dihydro-5H-pyrimido[5,4-b][1,4]diazepin-6(7H)-one (100 mg, 0.3238 mmol, prepared as described in WO 2007/095188) was dissolved in n-butyl alcohol (1 mL). To the butyl alcohol solution thus obtained were then added (1S)-1-phenylethanamine (750 μL, 5.830 mmol) and DIPEA (167.4 mg, 225.6 μL, 1.295 mmol). The resulting solution was heated at 140° C. in microwave for 90 minutes. Additional (1S)-1-phenylethanamine (500 μL, 3.887 mmol) was added and the reaction mixture heated for 90 minutes in microwave at 140° C. The solvent was removed in vacuo and the residue dissolved in dichloromethane and washed sequentially with 0.5M HCl (three times, 5 mL each), saturated aqueous sodium hydrogen carbonate solution (three times, 5 mL each), and brine (once, 5 mL). The washed solution was dried over MgSO4, filtered, and concentrated in vacuo to give yellow oil. The oil was purified by mass directed HPLC and the product fractions passed through a bicarbonate cartridge and lypholized to afford the title compound as a white solid (33.5 mg, 26% yield).

Source