Diisopropylcarbodiimide → (R)-1-(4-chlorobenzyl)-3-[{N-(3-bromo-4-methylbenzoyl)glycyl}amino]pyrrolidine

HRID 279257Notes

Reaction equation

HRID 279257 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[CH2:11][CH2:10][C@@H:9]([NH:12][C:13](=[O:16])[CH2:14][NH2:15])[CH2:8]2)=[CH:4][CH:3]=1.[Br:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][C:28]=1[CH3:29])[C:23](O)=[O:24].C(N=C=NC(C)C)(C)C.C1C=CC2N(O)N=NC=2C=1>C(Cl)(Cl)Cl.C(O)(C)(C)C>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[CH2:11][CH2:10][C@@H:9]([NH:12][C:13](=[O:16])[CH2:14][NH:15][C:23](=[O:24])[C:22]3[CH:26]=[CH:27][C:28]([CH3:29])=[C:20]([Br:19])[CH:21]=3)[CH2:8]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 821303-Bromo-4-methylbenzoic acidHCID 54551710(R)-1-(4-chlorobenzyl)-3-(glycylamino)pyrrolidine

Product 1

HCID 54170187(R)-1-(4-chlorobenzyl)-3-[{N-(3-bromo-4-methylbenzoyl)glycyl}amino]pyrrolidine

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6386tert-ButanolSolvent

Procedure

A solution of (R)-1-(4-chlorobenzyl)-3-(glycylamino)pyrrolidine (0.050 mmol) in CHCl3 (1.35 mL) and tert-butanol (0-15 mL) was treated with 3-bromo-4-methylbenzoic acid (0.060 mmol), diisopropylcarbodiimide (0.060 mmol), and HOBt (0.060 mmol). The reaction mixture was stirred at room temperature for 15 h. The mixture was loaded onto Varian™ SCX column, and washed with CH3OH/CHCl3 1:1 (12 mL) and CH3OH (12 mL). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated to afford (R)-1-(4-chlorobenzyl)-3-[{N-(3-bromo-4-methylbenzoyl)glycyl}amino]pyrrolidine (Compound No. 1098) (11.6 mg, 50%): The purity was determined by RPLC/MS (94%); ESI/MS m/e 466.0 (C21H23BrClN3O2).

Workup

  1. washwashed with CH3OH/CHCl3 1:1 (12 mL) and CH3OH (12 mL)
  2. washProduct was eluted off
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-40bfd0e71548420a91cae290143dc3f3
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Reaction notes

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