Acetonitrile → (R)-3-[[N-(2-amino-5-trifluoromethoxybenzoyl)glycyl]amino]-1-(2-amino-4-chlorobenzyl)pyrrolidine

HRID 133564Notes

Reaction equation

HRID 133564 reaction equation
[NH2:1][C:2]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][C:3]=1[C:4]([NH:6][CH2:7][C:8]([NH:10][C@@H:11]1[CH2:15][CH2:14][NH:13][CH2:12]1)=[O:9])=[O:5].[Cl:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Cl)=[C:28]([N+:34]([O-])=O)[CH:27]=1.C(#N)C>C(Cl)(Cl)Cl>[NH2:1][C:2]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:22])[F:23])=[CH:16][C:3]=1[C:4]([NH:6][CH2:7][C:8]([NH:10][C@@H:11]1[CH2:15][CH2:14][N:13]([CH2:30][C:29]2[CH:32]=[CH:33][C:26]([Cl:25])=[CH:27][C:28]=2[NH2:34])[CH2:12]1)=[O:9])=[O:5]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 5983994-Chloro-1-(chloromethyl)-2-nitrobenzeneHCID 11313986(R)-3-[2-(2-amino-5-trifluoromethoxybenzamido)acetamido]pyrrolidine

Product 1

HCID 69212491(R)-3-[[N-(2-amino-5-trifluoromethoxybenzoyl)glycyl]amino]-1-(2-amino-4-chlorobenzyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of (R)-3-[[N-(2-amino-5-trifluoromethoxybenzoyl)glycyl]amino]pyrrolidine (0.050 mmol) with 4-chloro-2-nitrobenzyl chloride (0.050 mmol), a piperidinomethylpolystyrene (60 mg), acetonitrile (1.0 mL) and chloroform (0.7 mL) was stirred at 50® C. overnight. The resulting reaction mixture was cooled, loaded onto a Varian™ SCX column and washed with 50% chloroform/methanol (10 mL) and methanol (10 mL). The obtained crude product was eluted with a solution of 2 M NH3 in methanol (5 mL) and concentrated. Ethanol (3 mL) and 10% palladium carbon were added to the resulting residue, and the solution was stirred at room temperature under a hydrogen atmosphere for 1.5 hours. The obtained solution was filtered, concentrated and then purified by preparative TLC to thereby provide (R)-3-[[N-(2-amino-5-trifluoromethoxybenzoyl)glycyl]amino]-1-(2-amino-4-chlorobenzyl)pyrrolidine (Compd. No. 1921) (2.2 mg, 6%). The purity was determined by RPLC/MS (81%). ESI/MS m/e 486.2 (M++H, C21H23ClF3N5O3).

Workup

  1. customovernight
  2. customThe resulting reaction mixture
  3. temperaturewas cooled
  4. washwashed with 50% chloroform/methanol (10 mL) and methanol (10 mL)
  5. customThe obtained crude product
  6. washwas eluted with a solution of 2 M NH3 in methanol (5 mL)
  7. concentrationconcentrated
  8. additionEthanol (3 mL) and 10% palladium carbon were added to the resulting residue
  9. filtrationThe obtained solution was filtered
  10. concentrationconcentrated
  11. custompurified by preparative TLC to thereby provide (R)-3-[[N-(2-amino-5-trifluoromethoxybenzoyl)glycyl]amino]-1-(2-amino-4-chlorobenzyl)pyrrolidine (Compd. No

Sources & evidence

ORD record
ord-898840d3077c4e778d3d3aa52b89bd8c
Source dataset
uspto-grants-2008_06
Patent number
US07390830B1

Reaction notes

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