1-Phenethylamine, (-)- → HCID 44595569, compound

HRID 1916084Notes

Reaction equation

HRID 1916084 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:21])[C:7](=[O:20])[C:8]([CH3:19])([CH3:18])[CH2:9][N:10]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[N:12]=1.[C:22]1([C@@H:28]([NH2:30])[CH3:29])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CCN(C(C)C)C(C)C>C(O)CCC>[CH:13]1([N:10]2[CH2:9][C:8]([CH3:19])([CH3:18])[C:7](=[O:20])[N:6]([CH3:21])[C:5]3[CH:4]=[N:3][C:2]([NH:30][C@H:28]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH3:29])=[N:12][C:11]2=3)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 758181-Phenethylamine, (-)-2×HCID 81531DiisopropylethylamineHCID 592951162-Chloro-9-cyclopentyl-5,7,7-trimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

Product 1

HCID 44595569HCID 44595569, compoundYield 26.3%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent2×

Conditions

Temperature
140 °C

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).

Workup

  1. temperaturethe reaction mixture heated for 90 minutes in microwave at 140° C
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue dissolved in dichloromethane
  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. dry with materialThe washed solution was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give yellow oil
  9. customThe oil was purified by mass

Sources & evidence

ORD record
ord-4858f0a619314a3ea0e779da323dce13
Source dataset
uspto-grants-2013_12
Patent number
US08618106B2

Reaction notes

Loading…