Iodo benzene diacetate → tert-butyl (3S)-1-((1R)-2,2,2-trifluoro-1-(3-(3-fluoro-7-(2-methoxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate

HRID 339097Notes

Reaction equation

HRID 339097 reaction equation
[F:1][C:2]([F:26])([F:25])[C@H:3]([N:12]1[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:13]1)[C:4]1[CH:5]=[N:6][C:7]([NH:10][NH2:11])=[CH:8][CH:9]=1.[F:27][C:28]1[C:29]([CH:43]=O)=[N:30][C:31]2[C:36]([CH:37]=1)=[CH:35][CH:34]=[C:33]([O:38][CH2:39][CH2:40][O:41][CH3:42])[CH:32]=2.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>CCO.C(Cl)Cl>[F:26][C:2]([F:25])([F:1])[C@H:3]([N:12]1[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:23])[CH3:21])[CH2:13]1)[C:4]1[CH:9]=[CH:8][C:7]2[N:6]([C:43]([C:29]3[C:28]([F:27])=[CH:37][C:36]4[C:31](=[CH:32][C:33]([O:38][CH2:39][CH2:40][O:41][CH3:42])=[CH:34][CH:35]=4)[N:30]=3)=[N:11][N:10]=2)[CH:5]=1

Participants

6

Reactant 3

HCID 12217721Iodo benzene diacetateHCID 86707414tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamateHCID 867075593-Fluoro-7-(2-methoxyethoxy)quinoline-2-carbaldehyde

Product 1

HCID 86707560tert-butyl (3S)-1-((1R)-2,2,2-trifluoro-1-(3-(3-fluoro-7-(2-methoxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamateYield 79.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate (0.080 g, 0.20 mmol) and 3-fluoro-7-(2-methoxyethoxy)quinoline-2-carbaldehyde (0.051 g, 0.20 mmol) in EtOH (10 mL) was stirred at ambient temperature for 3 hours. The solvent was removed. The residue obtained was dissolved in DCM (10 mL) and iodobenzene diacetate (0.078 g, 0.24 mmol) was added. The mixture was stirred at ambient temperature for 2 hours. The solvent was removed under reduced pressure. The residue obtained was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 10-90% CH3CN/water gradient; 25 CV)) to give tert-butyl (3S)-1-((1R)-2,2,2-trifluoro-1-(3-(3-fluoro-7-(2-methoxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate (0.096 g, 0.159 mmol, 78% yield) as a solid.

Workup

  1. customThe solvent was removed
  2. customThe residue obtained
  3. stirringThe mixture was stirred at ambient temperature for 2 hours
  4. customThe solvent was removed under reduced pressure
  5. customThe residue obtained
  6. customwas purified by C-18 reverse phase flash chromatography (Biotage SP4 unit

Sources & evidence

ORD record
ord-3de9fa6efd124f9797c2f89453f441ff
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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