1,2-Dichloroethane → 1-(tert-butoxycarbonyl)-3-isopropylprolyl-N-[5-chloro-2-(1H-1,2,4-triazol-1-yl)benzyl]-L-prolinamide

HRID 857760Notes

Reaction equation

HRID 857760 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH:13]([CH:16]([CH3:18])[CH3:17])[CH:9]1[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([N:35]2[CH:39]=[N:38][CH:37]=[N:36]2)=[C:24]([CH:34]=1)[CH2:25][NH:26][C:27](=[O:33])[C@@H:28]1[CH2:32][CH2:31][CH2:30][NH:29]1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(CC)CC>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH:13]([CH:16]([CH3:18])[CH3:17])[C@H:9]1[C:10]([N:29]1[CH2:30][CH2:31][CH2:32][C@H:28]1[C:27]([NH:26][CH2:25][C:24]1[CH:34]=[C:20]([Cl:19])[CH:21]=[CH:22][C:23]=1[N:35]1[CH:39]=[N:38][CH:37]=[N:36]1)=[O:33])=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 218661771-(tert-Butoxycarbonyl)-3-isopropyl-2-pyrrolidinecarboxylic acidHCID 69656007N-[5-chloro-2-(1H-1,2,4-triazol-1-yl)benzyl]-L-prolinamide

Product 1

HCID 696556661-(tert-butoxycarbonyl)-3-isopropylprolyl-N-[5-chloro-2-(1H-1,2,4-triazol-1-yl)benzyl]-L-prolinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(tert-butoxycarbonyl)-3-isopropyl-dl-proline, (77 mg, 0.30 mmol), N-[5-chloro-2-(1H1,2,4-triazol-1-yl)benzyl]-L-prolinamide (Example 27, Step B, 113 mg, 0.30 mmol), HOAt (20 mg, 0.15 mmol), EDC (86 mg, 0.45 mmol) and Et3N (80 μL, 0.60 mmol) in 1.5 mL DMF was stirred at room temperature. The diastereomeric products were separated by reverse phase HPLC (30 min gradient elution with 95:5 H2O/0.1% TFA:CH3CN/0.1% TFA to 5:95 H2O/0.1% TFA:CH3CN/0.1% TFA) and carried on directly to deprotection.

Workup

  1. customThe diastereomeric products were separated by reverse phase HPLC (30 min gradient elution with 95:5 H2O/0.1% TFA:CH3CN/0.1% TFA to 5:95 H2O/0.1% TFA:CH3CN/0.1% TFA)

Sources & evidence

ORD record
ord-7c1061318f7b40258fe19787052f28e2
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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