Sodium Bicarbonate → (S)-1-[N2-[3-(Benzoylamino)-2-oxo-4-phenylbutyl]-N6-[(1,1-dimethylethoxy)carbonyl]-L-lysyl]-L-proline, 1,1-dimethylethyl ester

HRID 485188Notes

Reaction equation

HRID 485188 reaction equation
[CH3:1][C:2]([CH3:38])([O:4][C:5]([NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C@@H:12]([C:24]([N:26]1[CH2:37][CH2:36][CH2:35][C@H:27]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[O:25])[NH:13][C:14](OCC1C=CC=CC=1)=O)=[O:6])[CH3:3].N1CCC[C@H]1C(OC(C)(C)C)=O.ClC[C:53](=[O:71])[C@@H:54]([NH:62][C:63](=[O:70])[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)[CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1.C(=O)(O)[O-].[Na+]>C(O)C.[Pd].CN(C)C=O>[C:63]([NH:62][CH:54]([CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C:53](=[O:71])[CH2:14][NH:13][C@H:12]([C:24]([N:26]1[CH2:37][CH2:36][CH2:35][C@H:27]1[C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])=[O:25])[CH2:11][CH2:10][CH2:9][CH2:8][NH:7][C:5]([O:4][C:2]([CH3:1])([CH3:38])[CH3:3])=[O:6])(=[O:70])[C:64]1[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 6453108L-Proline 1,1-dimethylethyl ester2×HCID 13339657(3S)-3-Benzoylamino-1-chloro-4-phenyl-2-butanoneHCID 14010667N-(Nalpha-benzyloxycarbonyl-Nepsilon-tert-butoxycarbonyl-L-lysyl)-L-proline tert-butyl ester

Product 1

HCID 57145955(S)-1-[N2-[3-(Benzoylamino)-2-oxo-4-phenylbutyl]-N6-[(1,1-dimethylethoxy)carbonyl]-L-lysyl]-L-proline, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

The ester product from part (a) is reduced in ethanol with palladium on carbon catalyst (10%) to yield 3.99 g. of 1-[N6 -[1,1-dimethylethoxy)carbonyl]-L-lysyl]L-proline, 1,1-dimethylethyl ester. This material is taken into 40 ml. of dimethylformamide and treated with (S)-N-[3-chloro-2-oxo-1-(phenylmethyl)propyl]benzamide (3.01 g.), from Example 63(b), and sodium bicarbonate (840 mg.). After stirring for 18 hours at room temperature, the reaction mixture is concentrated in vacuo, taken into ethyl acetate and washed with saturated sodium bicarbonate. The crude product (7.0 g.) is purified on a silica gel column eluting with ethyl acetate:1% methanol to give 1.7 g. of (S)-1-[N2 -[3-benzoylamino)-2-oxo-4-phenylbutyl]-N6 -[(1,1-dimethylethoxy)carbonyl]-L-lysyl]-L-proline, 1,1-dimethylethyl ester.

Workup

  1. customto yield 3.99 g
  2. concentrationthe reaction mixture is concentrated in vacuo
  3. washwashed with saturated sodium bicarbonate
  4. customThe crude product (7.0 g.) is purified on a silica gel column
  5. washeluting with ethyl acetate
  6. custom1% methanol to give 1.7 g

Sources & evidence

ORD record
ord-5a91f3c2da8b49e6a715c35b2ab8408a
Source dataset
uspto-grants-1985_08
Patent number
US04535176

Reaction notes

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