Diisopropylethylamine → 2-([N-methyl-N-{(1R)-1-(N-methyl-N-[(1R)-1-(methylcarbamoyl)-2-phenylethyl]carbamoyl)-2-(2-naphthyl)ethyl}carbamoyl]methoxymethyl)piperidin-1-carboxylic acid tert-butyl ester

HRID 495827

Reaction equation

HRID 495827 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][O:15][CH2:16][C:17]([OH:19])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:42][N:43]([CH:60]([C:68](=[O:71])[NH:69][CH3:70])[CH2:61][C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1)[C:44](=[O:59])[CH:45]([NH:57][CH3:58])[CH2:46][C:47]1[CH:56]=[CH:55][C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:48]=1.C(N(C(C)C)CC)(C)C>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][O:15][CH2:16][C:17](=[O:19])[N:57]([CH3:58])[C@@H:45]([C:44](=[O:59])[N:43]([CH3:42])[C@@H:60]([C:68](=[O:71])[NH:69][CH3:70])[CH2:61][C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1)[CH2:46][C:47]1[CH:56]=[CH:55][C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:48]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 108022172-Carboxymethoxymethyl-piperidine-1-carboxylic acid tert-butyl esterHCID 22326951N-methyl-2-methylamino-N-(1-methylcarbamoyl-2-phenylethyl)-3-(2-naphthyl)propionamide

Product 1

HCID 536855942-([N-methyl-N-{(1R)-1-(N-methyl-N-[(1R)-1-(methylcarbamoyl)-2-phenylethyl]carbamoyl)-2-(2-naphthyl)ethyl}carbamoyl]methoxymethyl)piperidin-1-carboxylic acid tert-butyl esterYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-(carboxymethoxymethyl)piperidine-1-carboxylic acid tert-butylester (225 mg, 0.82 mmol) in 5 ml of dichloromethane was added 1-hydroxy-7-azabenzotriazole (112 mg, 0.82 mmol) and 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride (173 mg, 0.90 mmol) and the mixture was to stirred for 30 min. N-Methyl-2-methylamino-N-(1-methylcarbamoyl-2-phenylethyl)-3-(2-naphthyl)propionamide (332 mg, 0.82 mmol) in dichloromethane (5mL) was added followed by diisopropylethylamine (0.14 ml, 0.82 mmol) and the mixture was stirred overnight at room temperature. The mixture was washed with water (5 ml) aqueous sodium bicarbonate (5 ml), water (2×5 ml), brine (5 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was chromatographed on silica (20 g) with ethyl acetate to give 416 mg of 2-([N-methyl-N-{(1R)-1-(N-methyl-N-[(1R)-1-(methylcarbamoyl)-2-phenylethyl]carbamoyl)-2-(2-naphthyl)ethyl}carbamoyl]methoxymethyl)piperidin-1-carboxylic acid tert-butyl ester.

Workup

  1. stirringthe mixture was stirred overnight at room temperature
  2. washThe mixture was washed with water (5 ml) aqueous sodium bicarbonate (5 ml), water (2×5 ml), brine (5 ml)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was chromatographed on silica (20 g) with ethyl acetate

Sources & evidence

ORD record
ord-3d1f838d9fe04e57b0ef39578e941597
Source dataset
uspto-grants-2005_09
Patent number
US06939880B2

Linked notes

Loading…