Triethylamine → HCID 178514012, compound

HRID 1284445Notes

Reaction equation

HRID 1284445 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][C@@H:4]([C:12]([OH:14])=O)[NH:3]1.ON1C(=O)CCC1=O.C1CCC(N=C=NC2CCCCC2)CC1.Cl.Cl.[NH2:40][C@H:41]([C:48]([N:50]1[C@H:54]([C:55]([NH2:57])=[O:56])[CH2:53][S:52][CH2:51]1)=[O:49])[CH2:42][C:43]1[N:47]=[CH:46][NH:45][CH:44]=1.C(N(CC)CC)C>CN(C=O)C>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][C@@H:4]([C:12]([NH:40][C@H:41]([C:48]([N:50]2[C@H:54]([C:55]([NH2:57])=[O:56])[CH2:53][S:52][CH2:51]2)=[O:49])[CH2:42][C:43]2[N:47]=[CH:46][NH:45][CH:44]=2)=[O:14])[NH:3]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 6363483HCID 6363483, compoundHCID 178478852HCID 178478852, compound

Product 1

HCID 178514012HCID 178514012, compoundYield 43.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Separately, (3S)-1-oxo-1,2,3,4-tetrahyroisoquinoline-3-carboxylic acid (70 mg, 0.36 mmole) and N-hydroxysuccinimide (41 mg, 0.36 mmole) are dissolved in DMF (5 ml) and thereto is added DCC (74 mg, 0.36 mmole) under ice-cooling. The mixture is stirred for 1.5 hours. To the solution of the activated ester thus prepared are added the (4R)-3-(L-histidyl)-thiazolidine-4-carboxamide dihydrochloride (150 mg, 0.4 mmole) prepared above and triethylamine (0.21 ml, 0.8 mmole) under ice-cooling. The mixture is stirred at 8° C. for 24 hours. The precipitated DCU is filtered off, and the filtrate is concentrated under reduced pressure. The residue is dissolved in water, and the solution is adjusted to pH 8 with sodium bicarbonate and is passed through a column (2.3×26 cm) packed with CHP-20P resin. The column is washed with water (500 ml) and further with 30% methanol (one liter), and then the product is eluted with 50% methanol. The fractions being positive to Pauly reagent are collected, distilled to remove methanol, and then lyophilized to give (4R)-3-{Nα -[(3S)-1-oxo-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]-L-histidyl}-thiazolidine-4-carboxamide (70 mg, yield: 41.8%).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringThe mixture is stirred at 8° C. for 24 hours
  4. filtrationThe precipitated DCU is filtered off
  5. concentrationthe filtrate is concentrated under reduced pressure
  6. dissolutionThe residue is dissolved in water
  7. washThe column is washed with water (500 ml) and further with 30% methanol (one liter)
  8. washthe product is eluted with 50% methanol
  9. customare collected
  10. distillationdistilled
  11. customto remove methanol

Sources & evidence

ORD record
ord-58bcd5bb7c484fcbbcde2e3701e1dc31
Source dataset
uspto-grants-1986_01
Patent number
US04563306

Reaction notes

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