Pyridine → N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N,2-dimethylalanyl-N-[(3R,4S,5S)-3-methoxy-5-methyl-1-oxo-1-(pentafluorophenoxy)heptan-4-yl]-N-methyl-L-valinamide

HRID 74788Notes

Reaction equation

HRID 74788 reaction equation
FC(F)(F)CC(O[C:7]1[C:12]([F:13])=[C:11]([F:14])[C:10]([F:15])=[C:9]([F:16])[C:8]=1[F:17])=O.[CH:20]1[C:32]2[CH:31]([CH2:33][O:34][C:35]([N:37]([CH3:64])[C:38]([CH3:63])([C:40]([NH:42][C@H:43]([C:47]([N:49]([C@@H:51]([C@@H:59]([CH3:62])[CH2:60][CH3:61])[C@H:52]([O:57][CH3:58])[CH2:53][C:54]([OH:56])=[O:55])[CH3:50])=[O:48])[CH:44]([CH3:46])[CH3:45])=[O:41])[CH3:39])=[O:36])[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]=2[CH:23]=[CH:22][CH:21]=1.N1C=CC=CC=1>ClCCl>[CH:29]1[C:30]2[CH:31]([CH2:33][O:34][C:35]([N:37]([CH3:64])[C:38]([CH3:63])([C:40]([NH:42][C@H:43]([C:47]([N:49]([C@@H:51]([C@@H:59]([CH3:62])[CH2:60][CH3:61])[C@H:52]([O:57][CH3:58])[CH2:53][C:54](=[O:56])[O:55][C:7]3[C:8]([F:17])=[C:9]([F:16])[C:10]([F:15])=[C:11]([F:14])[C:12]=3[F:13])[CH3:50])=[O:48])[CH:44]([CH3:45])[CH3:46])=[O:41])[CH3:39])=[O:36])[C:32]3[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:25]=2[CH:26]=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 86762713N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N,2-dimethylalanyl-N-[(2R,3S,4S)-1-carboxy-2-methoxy-4-methylhexan-3-yl]-N-methyl-L-valinamideHCID 86762715Pentafluorophenyl 3,3,3-trifluoropropanoate

Product 1

HCID 86762714N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N,2-dimethylalanyl-N-[(3R,4S,5S)-3-methoxy-5-methyl-1-oxo-1-(pentafluorophenoxy)heptan-4-yl]-N-methyl-L-valinamideYield 98.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Pentafluorophenyl 3,3,3-trifluoropropanoate (2.44 mL, 13.4 mmol, 2.0 eq.) was added to a solution of #128 (4.18 g, 6.70 mmol, 1.0 eq.) in 50 mL of dichloromethane followed by pyridine (1.61 mL, 20.1 mmol, 3.0 eq.). Reaction was allowed to stir at room temperature for -12 hours. Reaction was concentrated in vacuo and the residue was purified by silica chromatography (Gradient: 0%-70% acetone in heptanes) producing #135 (5.2 g, 98%) as a white foam. LC-MS (Protocol Q1): m/z 812.1 [M+Na+] retention time=1.24 minutes.

Workup

  1. customReaction
  2. customReaction
  3. concentrationwas concentrated in vacuo
  4. customthe residue was purified by silica chromatography (Gradient: 0%-70% acetone in heptanes)

Sources & evidence

ORD record
ord-9615bbd6ee93434896cca8588d073640
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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