Diisopropylethylamine → 2-[2-(Azepane-1-sulfonylamino)-4-methyl-pentanoylamino]-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester

HRID 2230320Notes

Reaction equation

HRID 2230320 reaction equation
[C:1]([O:5][C:6](=[O:32])[CH:7]([NH:23][C:24](=[O:31])[CH:25]([NH2:30])[CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[N:33]1([S:40](Cl)(=[O:42])=[O:41])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1.C(N(CC)C(C)C)(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:32])[CH:7]([NH:23][C:24](=[O:31])[CH:25]([NH:30][S:40]([N:33]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1)(=[O:42])=[O:41])[CH2:26][CH:27]([CH3:28])[CH3:29])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:11][CH:10]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 16227387Azepane-1-sulfonyl chlorideHCID 540817292-(2-Amino-4-methyl-pentanoylamino)-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester

Product 1

HCID 700598922-[2-(Azepane-1-sulfonylamino)-4-methyl-pentanoylamino]-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of the product from Example AI ([S-(R*,R*)]-2-(2-amino-4-methyl-pentanoylamino)-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester) (220 mg, 0.50 mmol), homopiperidinesulfonyl chloride (110 mg, 0.55 mmol, prepared by the method of Von Geldem, et al., J. Med. Chem., 1996;39:968-981), N,N-diisopropylethylamine (129 mg, 1.00 mmol), and DMAP (20 mg) in DMF (1 mL) is stirred at room temperature for 72 hours, diluted with ethyl acetate, and washed with water, 1N HCl, saturated NaHCO3 solution and brine, dried over anhydrous sodium sulfate, and concentrated. The oily residue thus obtained was purified via flash chromatography (30% EtOAc/hexane) followed by preparative TLC (2 elutions, 30% EtOAc/Hexane) to afford 39 mg of a clear colorless oil which is dissolved in 0.5 mL CHCl3, diluted with 4 mL hexane, and maintained at 3° C. until crystallization occurred. The crystals are collected and weigh 10.1 mg (3%), mp=123-124° C.

Workup

  1. washwashed with water, 1N HCl, saturated NaHCO3 solution and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customThe oily residue thus obtained
  5. customwas purified via flash chromatography (30% EtOAc/hexane)

Sources & evidence

ORD record
ord-1d9dddcdc7bb445eae4730fbc9367a7d
Source dataset
uspto-grants-2002_07
Patent number
US06423689B1

Reaction notes

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