Triethylamine → methyl (2S)-2-[(3-{(2R)-2-[2-(3-chlorophenyl)-(2R)-2-hydroxyethylamino]propyl}-1H-indole-7-carbonyl)amino]-4-methyl-pentanoate

HRID 1351938Notes

Reaction equation

HRID 1351938 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([OH:26])[CH2:9][NH:10][C@H:11]([CH3:25])[CH2:12][C:13]2[C:21]3[C:16](=[C:17]([C:22](O)=[O:23])[CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:27][C@H:28]([C:33]([O:35][CH3:36])=[O:34])[CH2:29][CH:30]([CH3:32])[CH3:31].Cl.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([OH:26])[CH2:9][NH:10][C@H:11]([CH3:25])[CH2:12][C:13]2[C:21]3[C:16](=[C:17]([C:22]([NH:27][C@@H:28]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:33]([O:35][CH3:36])=[O:34])=[O:23])[CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2723695Leucine methyl ester hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 694577363-{(2R)-2-[2-(3-chlorophenyl)-(2R)-2-hydroxyethylamino]propyl}-1H-indole-7-carboxylic acid

Product 1

HCID 86604019methyl (2S)-2-[(3-{(2R)-2-[2-(3-chlorophenyl)-(2R)-2-hydroxyethylamino]propyl}-1H-indole-7-carbonyl)amino]-4-methyl-pentanoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-{(2R)-2-[2-(3-chlorophenyl)-(2R)-2-hydroxyethyl-amino]propyl}-1H-indole-7-carboxylic acid (22 mg, 0.059 mmol), L-Leu-OMe.HCl (107 mg, 0.59 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (113 mg, 0.59 mmol), 1-hydroxybenztriazole (80 mg, 0.59 mmol), triethylamine (164 μL, 1.18 mmol) in dimethylformamide (2 mL) is stirred at room temperature for 18 hours. The mixture is diluted with ethyl acetate, washed with a saturated aqueous sodium hydrogen carbonate solution, water, and a saturated brine, dried over sodium sulfate, and concentrated. The residue is purified by silica gel column chromatography (a saturated ammonia solution in chloroform) and preparative reversed phase HPLC (octadecylsilyl, trifluoroacetic acid/acetonitrile/water) to give the desired methyl (2S)-2-[(3-{(2R)-2-[2-(3-chlorophenyl)-(2R)-2-hydroxyethylamino]propyl}-1H-indole-7-carbonyl)amino]-4-methylpentanoate.trifluoroacetate (23 mg, yield: 63%).

Workup

  1. washwashed with a saturated aqueous sodium hydrogen carbonate solution, water
  2. dry with materiala saturated brine, dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue is purified by silica gel column chromatography (a saturated ammonia solution in chloroform) and preparative reversed phase HPLC (octadecylsilyl, trifluoroacetic acid/acetonitrile/water)

Sources & evidence

ORD record
ord-ab762275ac434d13a62706b0da8252e4
Source dataset
uspto-grants-2007_05
Patent number
US07217724B2

Reaction notes

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