(2S)-1-[(3R)-3-amino-4-phenylbutanoyl]-N-({5-chloro-2-[(cyclopropylcarbamoyl)methoxy]phenyl}methyl)pyrrolidine-2-carboxamide → 1-[(3R)-3-Amino-4-phenylbutanoyl]-N-{2-[2-(cyclopropylamino)-2-oxoethoxy]benzyl}-L-prolinamide

HRID 11420Notes

Reaction equation

HRID 11420 reaction equation
[NH2:1][C@H:2]([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:3][C:4]([N:6]1[CH2:29][CH2:28][CH2:27][C@H:7]1[C:8]([NH:10][CH2:11][C:12]1[CH:17]=[C:16](Cl)[CH:15]=[CH:14][C:13]=1[O:19][CH2:20][C:21]([NH:23][CH:24]1[CH2:26][CH2:25]1)=[O:22])=[O:9])=[O:5].[H][H]>CO.[OH-].[OH-].[Pd+2]>[NH2:1][C@H:2]([CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[CH2:3][C:4]([N:6]1[CH2:29][CH2:28][CH2:27][C@H:7]1[C:8]([NH:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:19][CH2:20][C:21]([NH:23][CH:24]1[CH2:26][CH2:25]1)=[O:22])=[O:9])=[O:5]

Participants

5

Reactant 2

HCID 10164624(2S)-1-[(3R)-3-amino-4-phenylbutanoyl]-N-({5-chloro-2-[(cyclopropylcarbamoyl)methoxy]phenyl}methyl)pyrrolidine-2-carboxamideHCID 178418361HCID 178418361, compound

Product 1

HCID 102773771-[(3R)-3-Amino-4-phenylbutanoyl]-N-{2-[2-(cyclopropylamino)-2-oxoethoxy]benzyl}-L-prolinamideYield 71.5%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent2×

Procedure

Palladium hydroxide on activated charcoal (˜50 mg) was added to a solution of 15 mg of 1-[(3R)-3-amino-4-phenylbutanoyl]-N-{5-chloro-2-[2-(cyclopropylamino)-2-oxoethoxy]benzyl }-L-prolinamide in 1 mL methanol and the mixture was stirred under a balloon of hydrogen for 6 h. The reaction was diluted with methanol, filtered through a pad of Celite, and concentrated in vacuo. Purification using preparative TLC (silica gel, 13.5:1.5:85 methanol:concentrated ammonium hydroxide:methylene chloride) afforded 10 mg of the title compound. 1H NMR (400 MHz, CD3OD) δ 7.33–7.10 (m, 7H), 7.01–6.83 (d, 2H), 4.58–4.22 (m, 5H), 3.61–3.35 (m, 3H), 2.84–2.48 (m, 4H), 2.38–2.08 (m, 2H), 2.05–1.80 (m, 3H), 0.78–0.60 (m, 4H).

Workup

  1. filtrationfiltered through a pad of Celite
  2. concentrationconcentrated in vacuo
  3. customPurification

Sources & evidence

ORD record
ord-b307f8696e4749439cc0b1517f8db6d3
Source dataset
uspto-grants-2006_08
Patent number
US07098239B2

Reaction notes

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