Acetonitrile → (R)-3-[[N-(2-amino-5-(trifluoromethoxy)benzoyl]glycyl]amino]-1-(2,4-dichlorobenzyl)pyrrolidine

HRID 133563Notes

Reaction equation

HRID 133563 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]=[C:32]([Cl:34])[CH:31]=[CH:30][C:27]=1[CH2:28]Cl.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]([CH2:28][C:27]2[CH:30]=[CH:31][C:32]([Cl:34])=[CH:33][C:26]=2[Cl:25])[CH2:12]1)=[O:9])=[O:5]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 72122,4-Dichlorobenzyl chlorideHCID 11313986(R)-3-[2-(2-amino-5-trifluoromethoxybenzamido)acetamido]pyrrolidine

Product 1

HCID 54361675(R)-3-[[N-(2-amino-5-(trifluoromethoxy)benzoyl]glycyl]amino]-1-(2,4-dichlorobenzyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of (R)-3-[[N-(2-amino-5-(trifluoromethoxyl)benzoyl)glycyl]amino]pyrrolidine (0.050 mmol) with 2,4-dichlorobenzyl chloride (0.066 mL), a piperidinomethylpolystyrene (60 mg), acetonitrile (0.8 mL) and chloroform (0.5 mL) was stirred at 60° C. for 12 hours. The resulting reaction mixture was cooled to room temperature, loaded onto a Varian™ SCX column and washed with a 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. A 1,4-dioxane (2 mL) solution of 4 M HCl was added to the resulting residue, and the obtained mixture was stirred at room temperature overnight, concentrated and then purified by preparative TLC to afford (R)-3-[[N-(2-amino-5-(trifluoromethoxy)benzoyl]glycyl]amino]-1-(2,4-dichlorobenzyl)pyrrolidine (Compd. No. 1905) (17.6 mg, 70%). The purity was determined by RPLC/MS (93%). ESI/MS m/e 505 (M++H, C21H21Cl2F3N4O3).

Workup

  1. customThe resulting reaction mixture
  2. washwashed with a 50% chloroform/methanol (10 mL) and methanol (10 mL)
  3. customThe obtained crude product
  4. washwas eluted with a solution of 2 M NH3 in methanol (5 mL)
  5. concentrationconcentrated
  6. additionA 1,4-dioxane (2 mL) solution of 4 M HCl was added to the resulting residue
  7. concentrationconcentrated
  8. custompurified by preparative TLC

Sources & evidence

ORD record
ord-405b9d2fdc4b4495acb68d1e2357feba
Source dataset
uspto-grants-2008_06
Patent number
US07390830B1

Reaction notes

Loading…