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

HRID 339063Notes

Reaction equation

HRID 339063 reaction equation
[CH3:1][C@:2]1([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:6][CH2:5][N:4]([C@@H:7]([C:12]2[CH:13]=[N:14][C:15]([NH:18][NH2:19])=[CH:16][CH:17]=2)[C:8]([F:11])([F:10])[F:9])[CH2:3]1.[Si]([O:35][CH2:36][CH2:37][O:38][C:39]1[CH:48]=[C:47]2[C:42]([CH:43]=[CH:44][C:45]([CH:49]=O)=[N:46]2)=[CH:41][C:40]=1F)(C(C)(C)C)(C)C.[C:52](O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>CCO>[CH3:1][C@:2]1([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:6][CH2:5][N:4]([C@@H:7]([C:12]2[CH:17]=[CH:16][C:15]3[N:14]([C:49]([C:45]4[CH:44]=[CH:43][C:42]5[C:47](=[CH:48][C:39]([O:38][CH2:37][CH2:36][O:35][CH3:52])=[CH:40][CH:41]=5)[N:46]=4)=[N:19][N:18]=3)[CH:13]=2)[C:8]([F:9])([F:10])[F:11])[CH2:3]1

Participants

5

Reactant 3

HCID 12217721Iodo benzene diacetateHCID 86707435tert-butyl (S)-3-methyl-1-((S)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamateHCID 867075467-(2-(Tert-butyldimethylsilyloxy)ethoxy)-6-fluoroquinoline-2-carbaldehyde

Product 1

HCID 86707539tert-butyl (S)-3-methyl-1-((S)-2,2,2-trifluoro-1-(3-(7-(2-methoxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamateYield 60.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of tert-butyl (S)-3-methyl-1-((S)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate (1.50 g, 4.01 mmol), 7-(2-(tert-butyldimethylsilyloxy)ethoxy)-6-fluoroquinoline-2-carbaldehyde (1.40 g, 4.01 mmol) and EtOH (30 mL) was stirred at ambient temperature overnight. The solvent was removed under reduced pressure. The residue was dissolved in DCM (30 mL) and iodobenzene diacetate (1.68 g, 5.21 mmol) was added. The reaction mixture was stirred at ambient temperature overnight. The mixture was partitioned between EtOAc and saturated aqueous NaHCO3 solution. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (EtOAc) to give tert-butyl (S)-3-methyl-1-((S)-2,2,2-trifluoro-1-(3-(7-(2-methoxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate (1.45 g, 51%).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in DCM (30 mL)
  3. stirringThe reaction mixture was stirred at ambient temperature overnight
  4. customThe mixture was partitioned between EtOAc and saturated aqueous NaHCO3 solution
  5. extractionThe aqueous layer was extracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel (EtOAc)

Sources & evidence

ORD record
ord-c2bd7e14ebbe4cf69f7bc8623be30e6a
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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