Triethylamine → HCID 178472444, compound

HRID 1087977Notes

Reaction equation

HRID 1087977 reaction equation
[C:1]([O:5][C:6](=[O:33])[CH:7]([CH2:17][N:18]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:8][C:9]1([C:14](O)=[O:15])[CH2:13][CH2:12][CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.[CH2:64]([O:66][C:67]([C@H:69]1[CH2:74][CH2:73][C@@H:72]([NH2:75])[CH2:71][CH2:70]1)=[O:68])[CH3:65]>ClCCl>[C:1]([O:5][C:6](=[O:33])[CH:7]([CH2:17][N:18]([CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:8][C:9]1([C:14](=[O:15])[NH:75][C@H:72]2[CH2:71][CH2:70][C@@H:69]([C:67]([O:66][CH2:64][CH3:65])=[O:68])[CH2:74][CH2:73]2)[CH2:10][CH2:11][CH2:12][CH2:13]1)([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 221554593-(1-Carboxycyclopentyl)-2(dibenzylaminomethyl)propanoic acid t-butyl esterHCID 178472435HCID 178472435, compound

Product 1

HCID 178472444HCID 178472444, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The t-butyl ester from step (b) above (11.97 g, 26.54 mmole) in dry dichloromethane (200 ml), under nitrogen, was treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (10.19 g, 53 mmole), 1-hydroxybenztriazole (3.94 g, 29 mmole), triethylamine (16.08 g, 22.15 ml, 159 mmole) and cis-4-aminocyclohexane-carboxylic acid ethyl ester hydrochloride (6.04 g, 20 mmole). After stirring overnight at room temperature, the solvent was evaporated and the residue partitioned between ethyl acetate and water. The organic phase was washed with dilute hydrochloric acid (2×), dilute aqueous sodium bicarbonate, water, dried (Na2SO4) and evaporated to yield the crude product (15.5 g). This was chromatographed on silica (400 g) eluting with 1 to 10% diethyl ether in dichloromethane. Evaporation of the desired fractions gave 3-{1-[(cis-4-ethoxycarbonyl-cyclohexyl)-carbamoyl]cyclopentyl}-2-(dibenzylaminomethyl)propanoic acid t-butyl ester as an oil (11.43 g, 71%). Found: C,73.38; H,8.87; N,4.42. C37H52N2O5 requires C,73.48; H,8.67; N,4.68%.

Workup

  1. customthe solvent was evaporated
  2. customthe residue partitioned between ethyl acetate and water
  3. washThe organic phase was washed with dilute hydrochloric acid (2×), dilute aqueous sodium bicarbonate, water
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customto yield the crude product (15.5 g)
  7. customThis was chromatographed on silica (400 g)
  8. washeluting with 1 to 10% diethyl ether in dichloromethane
  9. customEvaporation of the desired fractions

Sources & evidence

ORD record
ord-c2483023aa5a41189877e1da9c7a7f55
Source dataset
uspto-grants-1990_10
Patent number
US04960792

Reaction notes

Loading…