Pyridine → 1,2-dimethyl-L-prolyl-N-[(3R,4S,5S)-3-methoxy-5-methyl-1-oxo-1-(pentafluorophenoxy)heptan-4-yl]-N-methyl-L-valinamide

HRID 74813Notes

Reaction equation

HRID 74813 reaction equation
[CH3:1][N:2]1[CH2:29][CH2:28][CH2:27][C@@:3]1([CH3:30])[C:4]([NH:6][C@H:7]([C:11]([N:13]([C@@H:15]([C@@H:23]([CH3:26])[CH2:24][CH3:25])[C@H:16]([O:21][CH3:22])[CH2:17][C:18]([OH:20])=[O:19])[CH3:14])=[O:12])[CH:8]([CH3:10])[CH3:9])=[O:5].N1C=CC=CC=1.FC(F)(F)C(O[C:42]1[C:47]([F:48])=[C:46]([F:49])[C:45]([F:50])=[C:44]([F:51])[C:43]=1[F:52])=O>ClCCl>[CH3:1][N:2]1[CH2:29][CH2:28][CH2:27][C@@:3]1([CH3:30])[C:4]([NH:6][C@H:7]([C:11]([N:13]([C@@H:15]([C@@H:23]([CH3:26])[CH2:24][CH3:25])[C@H:16]([O:21][CH3:22])[CH2:17][C:18](=[O:20])[O:19][C:42]1[C:43]([F:52])=[C:44]([F:51])[C:45]([F:50])=[C:46]([F:49])[C:47]=1[F:48])[CH3:14])=[O:12])[CH:8]([CH3:10])[CH3:9])=[O:5]

Participants

5

Reactant 3

HCID 1049PyridineHCID 4327891Pentafluorophenyl TrifluoroacetateHCID 866857671,2-dimethyl-L-prolyl-N-[(2R,3S,4S)-1-carboxy-2-methoxy-4-methylhexan-3-yl]-N-methyl-L-valinamide

Product 1

HCID 866857681,2-dimethyl-L-prolyl-N-[(3R,4S,5S)-3-methoxy-5-methyl-1-oxo-1-(pentafluorophenoxy)heptan-4-yl]-N-methyl-L-valinamideYield 125.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a cooled solution (0° C.) of #203 (7.0 g, 10.77 mmol, 1 eq.) in dichloromethane (15 mL) was added dropwise pyridine (3.41 g 43.08 mmol, 4 eq.) followed by a solution of pentafluorophenyl trifluoroacetate (6.03 g, 21.54 mmol, 2 eq.) in dichloromethane (7 mL). The mixture was stirred at room temperature for one hour, and the solvent was concentrated in vacuo. The residue was purified by silica gel chromatography (Gradient: 1 to 10% methanol in dichloromethane) to afford compound #204 (8 g, 82% over two steps) as yellow solid.

Workup

  1. concentrationthe solvent was concentrated in vacuo
  2. customThe residue was purified by silica gel chromatography (Gradient: 1 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-233651c6e58345c691b869d34f9be8c5
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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