Diisopropylethylamine → 3-(4-Benzyloxy-phenyl)-2-[4-methyl-2-(morpholine-4-sulfonylamino)-pentanoylamino]-propionic acid tert-butyl ester

HRID 2230322Notes

Reaction equation

HRID 2230322 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:39](Cl)(=[O:41])=[O:40])[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.C(N(CC)C(C)C)(C)C>CN(C1C=CN=CC=1)C.C1C=CC=CC=1>[C:1]([O:5][C:6](=[O:32])[CH:7]([NH:23][C:24](=[O:31])[CH:25]([NH:30][S:39]([N:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1)(=[O:41])=[O:40])[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

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 12798265Morpholine-4-sulfonyl chlorideHCID 540817292-(2-Amino-4-methyl-pentanoylamino)-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester

Product 1

HCID 700611183-(4-Benzyloxy-phenyl)-2-[4-methyl-2-(morpholine-4-sulfonylamino)-pentanoylamino]-propionic acid tert-butyl esterYield 65%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 241BenzeneSolvent

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) (397 mg, 0.90 mmol), morpholine-4-sulphonyl chloride (334 mg, 1.8 mmol, prepared by the method of von Geldem, et al., J. Med. Chem., 1996;39:968-981), N,N-diisopropylethyl-amine (246 mg, 1.9 mmol), and DMAP (25 mg) in benzene (5 mL) was heated under reflux for 3 hours, then concentrated in vacuo and the residue dissolved in ethyl acetate, and washed with saturated NaHCO3 solution, water and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The amber oil thus obtained was purified via flash chromatography (silica gel, 35% EtOAc/Hexane) to give 346 mg (65%) of the title compound as a yellow foam, mp=54-57° C.

Workup

  1. temperatureunder reflux for 3 hours
  2. concentrationconcentrated in vacuo
  3. dissolutionthe residue dissolved in ethyl acetate
  4. washwashed with saturated NaHCO3 solution, water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe amber oil thus obtained
  8. customwas purified via flash chromatography (silica gel, 35% EtOAc/Hexane)

Sources & evidence

ORD record
ord-39e6773876a340948784f1b127d6be19
Source dataset
uspto-grants-2002_07
Patent number
US06423689B1

Reaction notes

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