Sodium → HCID 178448659, compound

HRID 1792934Notes

Reaction equation

HRID 1792934 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 1 N 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 1 N 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-fa2e29fc363c4393b8c8453589380eb7
Source dataset
uspto-grants-2006_07
Patent number
US07078428B2

Reaction notes

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