Piperidine → HCID 59977285, compound

HRID 2270841Notes

Reaction equation

HRID 2270841 reaction equation
N1CCCCC1.C1C2C(COC([NH:24][CH2:25][C@@H:26]([C:50]([O:52][CH3:53])=[O:51])[NH:27][C:28](=[O:49])[C:29]3[CH:34]=[CH:33][C:32]([C:35]([NH:37][CH2:38][C:39]4[CH:47]=[CH:46][CH:45]=[C:44]5[C:40]=4[CH:41]=[CH:42][NH:43]5)=[O:36])=[CH:31][C:30]=3[Cl:48])=O)C3C(=CC=CC=3)C=2C=CC=1>CN(C)C=O>[NH2:24][CH2:25][C@@H:26]([C:50]([O:52][CH3:53])=[O:51])[NH:27][C:28](=[O:49])[C:29]1[CH:34]=[CH:33][C:32]([C:35]([NH:37][CH2:38][C:39]2[CH:47]=[CH:46][CH:45]=[C:44]3[C:40]=2[CH:41]=[CH:42][NH:43]3)=[O:36])=[CH:31][C:30]=1[Cl:48]

Participants

4

Reactant 2

HCID 8082PiperidineHCID 131723033HCID 131723033, compound

Product 1

HCID 59977285HCID 59977285, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Piperidine (88 pL, 0.89 mmol) was added to a solution of 3-[(9H-fluoren-9-ylmethoxy) carbonyl]amino-N-[2-chloro-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-L-alanine, methyl ester (116 mg, 0.18 mmol) in N,N-dimethylformamide (5 mL). The solution was stirred at room temperature for 30 min and then the solvent was evaporated. The resulting white solid was triturated with ether five times and dried in vacuo to give 3-amino-N-[2-chloro-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-L-alanine, methyl ester as an off-white solid (59 mg, 81%). N,N-Dimethylformamide (5 mL) was added, followed by HOAT (23 mg, 0.17 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (32 mg, 0.17 mmol), and thiophene-2-carboxylic acid (18 mg, 0.14 mmol). The reaction mixture was stirred at room temperature for 18 h. Water was added, and the mixture was extracted three times with ethyl acetate. The combined extracts were washed with brine, dried (Na2SO4), filtered, evaporated, and chromatographed (40-80% ethyl acetate/hexanes) to give 3-[(thiophene-2-carbonyl)amino)-N-[2-chloro-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-L-alanine, methyl ester (58 mg, 78%). A solution of lithium hydroxide monohydrate (13 mg, 0.32 mmol) in tetrahydrofuran/methanol/water (3:1:1) was added, and the solution was stirred at room temperature for 20 min. The solvent was evaporated and the residue was purified by HPLC to give 3-(thiophene-2-carbonyl)amino-N-[2-chloro-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-L-alanine (45 mg, 80% from ester, 48% for three steps) as a white powder.

Workup

  1. customthe solvent was evaporated
  2. customThe resulting white solid was triturated with ether five times
  3. customdried in vacuo

Sources & evidence

ORD record
ord-f6f9e13fda0a46419af01148e98949b9
Source dataset
uspto-grants-2001_12
Patent number
US06331640B1

Reaction notes

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