Sodium → HCID 178448659, compound

HRID 733244Notes

Reaction equation

HRID 733244 reaction equation
[Na].[Cl-].[NH2:3][C:4]([NH2:6])=[NH2+:5].[CH:7]([O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[CH:16]([CH2:20][C:21](OCC)=[O:22])[N:15]([CH2:26][CH:27]([CH3:29])[CH3:28])[C:14]2=[O:30])([CH3:9])[CH3:8]>C(O)C>[CH2:26]([N:15]1[C:14](=[O:30])[C:13]2[C:17](=[CH:18][CH:19]=[C:11]([O:10][CH:7]([CH3:8])[CH3:9])[CH:12]=2)[CH:16]1[CH2:20][C:21]([NH:5][C:4]([NH2:6])=[NH:3])=[O:22])[CH:27]([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 5360545SodiumHCID 5460839Carbamimidoylazanium ChlorideHCID 86591367ethyl (5-isopropyloxy-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate

Product 1

HCID 178448659HCID 178448659, compoundYield 4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

N-[2-(2-Isobutyl-5-isopropoxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-acetyl]-guanidine is prepared as described in Example 9, starting with 20 cm3 of absolute ethanol, 0.086 g of sodium, 0.36 g of guanidinium chloride and 0.42 g of ethyl (5-isopropyloxy-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate. The reaction mixture is stirred at a temperature in the region of 20° C. for 18 hours and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is then taken up in 50 cm3 of ethyl acetate and the organic phase is washed twice with 30 cm3 of aqueous 1N sodium hydroxide solution and then twice with 50 cm3 of aqueous 1N hydrochloric acid solution. The acidic aqueous phase is treated with aqueous 30% sodium hydroxide solution to pH 14, and then extracted with 3 times 30 cm3 of ethyl acetate. The organic extracts are combined, washed with 50 cm3 of saturated brine, dried over magnesium sulfate and concentrated under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is triturated with diethyl ether and then filtered and dried in a desiccator under reduced pressure (2 Pa) at a temperature in the region of 40° C. for 2 hours. 0.0175 g of N-[2-(2-Isobutyl-5-isopropoxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-acetyl]-guanidine is thus obtained in the form of a white powder melting at 208° C. 1H NMR (300 MHz, d6-(CD3)2SO, δ in ppm): 0.75 (d, J=6.5 Hz: 3H); 0.90 (d, J=6.5 Hz: 3H); 1.30 (mt: 6H); 2.01 (mt: 1H); 2.40 (dd, J=15 and 6.5 Hz: 1H); 2.65 (dd, J=15 and 6.5 Hz: 1H); 3.00 (dd, J=13.5 and 5.5 Hz: 1H); 3.53 (dd, J=13.5 and 10 Hz: 1H) 4.68 (mt: 1H); 4.96 (broad t, J=6.5 Hz: 1H); from 6.40 to 7.10 (broad multiplet: 2H); 6.98 (dd, J=8.5 and 2 Hz: 1H); 7.09 (d, J=2 Hz: 1H); 7.54 (d, J=8.5 Hz: 1H); from 7.60 to 8.20 (broad multiplet: 2H).

Workup

  1. customN-[2-(2-Isobutyl-5-isopropoxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-acetyl]-guanidine is prepared
  2. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  3. washthe organic phase is washed twice with 30 cm3 of aqueous 1N sodium hydroxide solution
  4. additionThe acidic aqueous phase is treated with aqueous 30% sodium hydroxide solution to pH 14
  5. extractionextracted with 3 times 30 cm3 of ethyl acetate
  6. washwashed with 50 cm3 of saturated brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure (2 kPa) at a temperature in the region of 40° C
  9. customThe residue is triturated with diethyl ether
  10. filtrationfiltered
  11. customdried in a desiccator under reduced pressure (2 Pa) at a temperature in the region of 40° C. for 2 hours

Sources & evidence

ORD record
ord-6d0328214584463e8834c21a3b9ffd88
Source dataset
uspto-grants-2009_09
Patent number
US07589117B2

Reaction notes

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