Triethylamine → HCID 178472439, compound

HRID 1086729Notes

Reaction equation

HRID 1086729 reaction equation
[C:1]([O:5][C:6](=[O:45])[CH:7]([CH2:28][C:29]1[CH:34]=CC=[C:31](C(OCC2C=CC=CC=2)=O)[CH:30]=1)[CH2:8][C:9]1([C:14](=[O:27])[NH:15][C@H:16]2[CH2:21][CH2:20][C@@H:19]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH2:13][CH2:12][CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].Cl.C(N=C=N[CH2:52][CH2:53][CH2:54][N:55]([CH3:57])C)C.[OH:58]N1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN>O1CCCC1.[Pd].C(Cl)Cl.C(OCC)(=O)C.CO>[C:1]([O:5][C:6](=[O:45])[CH:7]([CH2:28][C:29]1[CH:30]=[CH:31][CH:52]=[C:53]([C:54](=[O:58])[NH:55][CH3:57])[CH:34]=1)[CH2:8][C:9]1([C:14](=[O:27])[NH:15][C@H:16]2[CH2:17][CH2:18][C@@H:19]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:20][CH2:21]2)[CH2:13][CH2:12][CH2:11][CH2:10]1)([CH3:3])([CH3:2])[CH3:4]

Participants

11

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 178472440HCID 178472440, compound

Product 1

HCID 178472439HCID 178472439, compoundYield 80%

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-{1-[(cis-4-Ethoxycarbonylcyclohexyl)carbamoyl]cyclopentyl}-2-[3-(benzyloxycarbonyl)phenylmethyl]propanoic acid tert-butyl ester (370 mg, 0.60 mmole) was dissolved in tetrahydrofuran (30 ml) and was stirred with 5% palladium on carbon catalyst (50 mg) under an atmosphere of hydrogen at 50 p.s.i. (3.45 bar) for 5 hours. Further catalyst (50 mg) was added and the hydrogenation was continued for 48 hours. The catalyst was removed by filtration and the solvent evaporated to give a yellow oil. Chromatography on silica gel eluting with a mixture of methanol and ethyl acetate (1:4 to 1:1 by volume) gave a colourless oil. The oil (240 mg) was added to a solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (170 mg, 0.91 mmole), 1-hydroxybenzotriazole (140 mg, 0.91 mmole), triethylamine (182 mg, 1.80 mmole) and methylamine hydrochloride (31 mg, 0.45 mmole) in dry methylene chloride (20 ml), and the mixture was stirred at room temperature for 6 days. The solvent was evaporated under reduced pressure and the residue partitioned between ethyl acetate and water. The aqueous layer was acidified with 2N hydrochloric acid, separated and extracted three times with ethyl acetate. The organic fractions were combined and washed sequentially with saturated aqueous sodium bicarbonate solution, water and brine. Drying (MgSO4) and evaporation under reduced pressure gave a yellow oil which was chromatographed on silica gel eluting with a mixture of ethyl acetate and pentane (1:1 by volume). Azeotroping with methylene chloride gave the desired amide as a colourless oil (200 mg, 80%). Found: C,67.58; H,8.80; N,5.22. C31H46N2O6.1/8 CH2Cl2 requires: C,67.57; H,8.42; N,5.06%.

Workup

  1. waitthe hydrogenation was continued for 48 hours
  2. customThe catalyst was removed by filtration
  3. customthe solvent evaporated
  4. customto give a yellow oil
  5. customgave a colourless oil
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue partitioned between ethyl acetate and water
  8. customseparated
  9. extractionextracted three times with ethyl acetate
  10. washwashed sequentially with saturated aqueous sodium bicarbonate solution, water and brine
  11. customDrying
  12. custom(MgSO4) and evaporation under reduced pressure
  13. customgave a yellow oil which
  14. customwas chromatographed on silica gel eluting with a mixture of ethyl acetate and pentane (1:1 by volume)
  15. customAzeotroping with methylene chloride

Sources & evidence

ORD record
ord-778bbb9344b645f2a556e13621a68564
Source dataset
uspto-grants-1991_07
Patent number
US05030654

Reaction notes

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