1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid (1H-tetrazol-5-ylmethyl)-amide

HRID 1264402Notes

Reaction equation

HRID 1264402 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11]([N:14]1[CH2:18][C@H:17]([S:19][C:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:16][C@H:15]1[C:39](O)=[O:40])(=[O:13])=[O:12].ON1C=CC=CC1=O.CCN=C=NCCCN(C)C.[NH2:61][CH2:62][C:63]1[NH:67][N:66]=[N:65][N:64]=1>C(Cl)Cl.CN(C=O)C>[NH:64]1[C:63]([CH2:62][NH:61][C:39]([C@@H:15]2[CH2:16][C@@H:17]([S:19][C:20]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:18][N:14]2[S:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)(=[O:12])=[O:13])=[O:40])=[N:67][N:66]=[N:65]1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69975HydroxypyridinoneHCID 69428772(2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acidHCID 178510704HCID 178510704, compound

Product 1

HCID 178523106(2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid (1H-tetrazol-5-ylmethyl)-amideYield 44.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 200 mg (0.34 mmol) (2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid and 42 mg (0.38 mmol) N-hydroxy-2-pyridone in 15 ml CH2Cl2 were treated at 0° C. with 72 mg (0.38 mmol) of EDCI. After 3.5h at RT, it was cooled (0° C.) and treated with 37 mg (0.38 mmol) of 5-aminomethyl-tetrazol. The reaction was stirred over night at RT, 2 ml DMF were added and after 4 h at RT the reaction was extracted with EtOAc/aqueous saturated NaHCO3. The organic phase was washed with aqueous 10% KHSO4, dried over Na2SO4 and purified by flash-chromatography on silicagel (CH2Cl2/MeOH 9:1) to give 100 mg (44%) of (2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid (1H-tetrazol-5-ylmethyl)-amide, mp: 135-145 slow dec, MS: 661 (MH+).

Workup

  1. extractionwas extracted with EtOAc/aqueous saturated NaHCO3
  2. washThe organic phase was washed with aqueous 10% KHSO4
  3. dry with materialdried over Na2SO4
  4. custompurified by flash-chromatography on silicagel (CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-facfe0a460f3426d9cdf4a8f4e5d7dbb
Source dataset
uspto-grants-2003_04
Patent number
US06541638B2

Reaction notes

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