Ethanolamine → N-(2-hydroxyethyl)-4-[(S)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidin-1-yl]benzamide

HRID 1811626Notes

Reaction equation

HRID 1811626 reaction equation
[NH2:1][CH2:2][CH2:3][OH:4].Cl.[C:6]1([C@H:16]([NH:18][C@H:19]2[CH2:23][CH2:22][N:21]([C:24]3[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=3)[CH2:20]2)[CH3:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8][CH:7]=1.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl>CN(C)C=O.C(N(CC)CC)C>[OH:4][CH2:3][CH2:2][NH:1][C:28](=[O:29])[C:27]1[CH:31]=[CH:32][C:24]([N:21]2[CH2:22][CH2:23][C@H:19]([NH:18][C@@H:16]([C:6]3[C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[CH:9]=[CH:8][CH:7]=3)[CH3:17])[CH2:20]2)=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 700EthanolamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 674072274-[(S)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidin-1-yl]benzoic acid hydrochloride2×

Product 1

HCID 58973499N-(2-hydroxyethyl)-4-[(S)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidin-1-yl]benzamideYield 44.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a mixed solution of 7.7 mg of 2-aminoethanol and 50 mg of 4-[(S)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidin-1-yl]benzoic acid hydrochloride (the compound obtained in Example 3.001) dissolved in 8 ml of dimethylformamide were added 22.2 mg of 1-hydroxybenzotriazole, 70 μl of triethylamine and 31.4 mg of EDC hydrochloride, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was evaporated, a saturated aqueous sodium bicarbonate solution and chloroform were added to the residue, and the mixture was stirred and the liquids were separated. The organic layer was dried and concentrated, and the residue was purified by NH thin layer silica gel chromatography (chloroform:methanol=39:1) and thin layer silica gel chromatography (chloroform:methanol=9:1) to give 22.6 mg of N-(2-hydroxyethyl)-4-[(S)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidin-1-yl]benzamide. (2) To a solution of 22.6 mg of N-(2-hydroxyethyl)-4-[(S)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidin-1-yl]-benzamide dissolved in 1 ml of methylene chloride was added dropwise 3 ml of a solution of 4M hydrochloric acid in dioxane, and the mixture was stirred for a while. The reaction mixture was evaporated; and, to the residue was added tert-butanol to dissolve the same, and freeze-dried to obtain 25.6 mg of N-(2-hydroxyethyl)-4-[(S)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidin-1-yl]benzamide hydrochloride (the following Table A3, Example 3.017).

Workup

  1. customThe reaction mixture was evaporated
  2. additiona saturated aqueous sodium bicarbonate solution and chloroform were added to the residue
  3. stirringthe mixture was stirred
  4. customthe liquids were separated
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. customthe residue was purified by NH thin layer silica gel chromatography (chloroform:methanol=39:1) and thin layer silica gel chromatography (chloroform:methanol=9:1)

Sources & evidence

ORD record
ord-2217ccebc9384bc8a4a9553bab6720e8
Source dataset
uspto-grants-2013_01
Patent number
US08362274B2

Reaction notes

Loading…