1-Hydroxybenzotriazole → 9-[Oxo-(3,4,5-trimethoxyphenyl)-acetyl]-3-(4-phenyl-butyl)-3,9-diaza-bicyclo[3.3.1]nonane-2,4-dione

HRID 987088Notes

Reaction equation

HRID 987088 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][N:11]2[C:18](=[O:19])[CH:17]3[NH:20][CH:13]([CH2:14][CH2:15][CH2:16]3)[C:12]2=[O:21])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O=[C:23]1[C:28]([O:29][CH3:30])=[C:27]([O:31][CH3:32])[C:26]([O:33][CH3:34])=[CH:25][CH:24]1[CH2:35][C:36]([OH:38])=O.C1C=CC2N([OH:48])N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[O:48]=[C:35]([C:24]1[CH:25]=[C:26]([O:33][CH3:34])[C:27]([O:31][CH3:32])=[C:28]([O:29][CH3:30])[CH:23]=1)[C:36]([N:20]1[CH:17]2[CH2:16][CH2:15][CH2:14][CH:13]1[C:12](=[O:21])[N:11]([CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:18]2=[O:19])=[O:38]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 229879053-(4-Phenylbutyl)-3,9-diaza-bicyclo[3.3.1]nonane-2,4-dione2×HCID 696972782-Oxo-3,4,5-trimethoxyphenylacetic acid

Product 1

HCID 229879039-[Oxo-(3,4,5-trimethoxyphenyl)-acetyl]-3-(4-phenyl-butyl)-3,9-diaza-bicyclo[3.3.1]nonane-2,4-dioneYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

3-(4-Phenylbutyl)-3,9-diaza-bicyclo[3.3.1]nonane-2,4-dione (Compound 14, 0.42 g, 1.47 mmol) and 2-oxo-3,4,5-trimethoxyphenylacetic acid (0.35 g, 1.47 mmol) were dissolved in CH2Cl2 (5 mL), and the solution was cooled to 0° C. HOBt (0.21 g, 1.54 mmol) was added, followed by EDC.HCl (0.30 g, 1.54 mmol) and TEA (0.15 g, 1.47 mmol). The reaction was allowed to reach room temperature and stirred for 5 hours. The volatiles were removed using a high-vacuum rotary evaporator. The residue was dissolved in EtOAc and washed with 10% citric acid solution (10 mL), followed by water (10 mL), saturated NaHCO3 (10 mL), and brine (10 mL). The combined organic layers were dried over Na2SO4 and were concentrated. Flash chromatographic purification of the residue (30% EtOAc/hexanes) gave Compound 15 as a pale-yellow solid (0.25 g, 34%, one isomer). mp=101-103° C.; Rf=0.32 (50% EtOAc/hexanes); IR: 2939, 2866, 1739, 1682, 1651, 1582, 1503, 1454, 1416, 1361, 1337, 1243, 1167, 1126, 1067, 991, 914, 862 cm−1; 1H NMR (major rotamer): δ 1.56-1.64 (m, 5H), 1.93-2.01 (m, 5H), 2.61-2.66 (m, 2H), 3.80-3.85 (m, 2H), 3.95 (s, 9H), 4.51 (brs, 1H), 5.46 (brs, 1H),7.14-7.29 (m, 7H); HRMS (M+H+): expected 509.2288, observed 509.2275; EA: calculated, C (66.13), H (6.34), N (5.51); found, C (66.00, H (6.37), N (5.50).

Workup

  1. customto reach room temperature
  2. customThe volatiles were removed
  3. customa high-vacuum rotary evaporator
  4. dissolutionThe residue was dissolved in EtOAc
  5. washwashed with 10% citric acid solution (10 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationwere concentrated
  8. customFlash chromatographic purification of the residue (30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1cea540ebd574f6fae8eefd4f36949dd
Source dataset
uspto-grants-2003_10
Patent number
US06630472B1

Reaction notes

Loading…