Lithium iodide → ((S)-1-{6-Bromo-1-[5-(4-fluoro-benzoyl)-pyridin-3-ylmethyl]-2-oxo-1,2-dihydro-pyridin-3-ylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester

HRID 556270Notes

Reaction equation

HRID 556270 reaction equation
[CH2:1]([O:8][C:9](=[O:25])[N:10]([C@H:12]([C:14](=[O:24])[NH:15][C:16]1[C:17](=[O:23])[NH:18][C:19]([Br:22])=[CH:20][CH:21]=1)[CH3:13])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-].[Li+].[F:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]([C:37]2[CH:38]=[N:39][CH:40]=[C:41]([CH2:43]Cl)[CH:42]=2)=[O:36])=[CH:31][CH:30]=1.C(N(C(C)C)CC)(C)C>O(C(OC)C)C.C(OCC)(=O)C>[CH2:1]([O:8][C:9](=[O:25])[N:10]([C@H:12]([C:14](=[O:24])[NH:15][C:16]1[C:17](=[O:23])[N:18]([CH2:43][C:41]2[CH:40]=[N:39][CH:38]=[C:37]([C:35](=[O:36])[C:32]3[CH:33]=[CH:34][C:29]([F:28])=[CH:30][CH:31]=3)[CH:42]=2)[C:19]([Br:22])=[CH:20][CH:21]=1)[CH3:13])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 66321Lithium iodideHCID 81531DiisopropylethylamineHCID 59200161[(S)-1-(6-Bromo-2-oxo-1,2-dihydro-pyridin-3-ylcarbamoyl)-ethyl]-methyl-carbamic acid benzyl esterHCID 59200177(5-Chloromethyl-pyridin-3-yl)-(4-fluoro-phenyl)-methanone

Product 1

HCID 59200196((S)-1-{6-Bromo-1-[5-(4-fluoro-benzoyl)-pyridin-3-ylmethyl]-2-oxo-1,2-dihydro-pyridin-3-ylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl esterYield 63%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 107951,1-DimethoxyethaneSolvent

Procedure

To a solution of [(S)-1-(6-bromo-2-oxo-1,2-dihydro-pyridin-3-ylcarbamoyl)-ethyl]-methyl-carbamic acid benzyl ester (1C) (100 mg, 0.25 mmol) in dimethoxylethane (DME) (3 mL) at room temperature, is added lithium iodide (36 mg, 0.27 mmol) in one portion. After being stirred at room temperature for 5 minutes, to the reaction mixture, is added 4-fluoro-phenyl-(5-chloromethyl-pyridin-3-yl)-methanone (IF) (80 mg, 0.32 mmol) in one portion. After being stirred at room temperature for 5 minutes, to the reaction mixture, is added drop wise diisopropylethylamine (DIPEA) (0.09 mL, 0.50 mmol). The reaction mixture is stirred at 60□C for 6 hours. The reaction solution is diluted with ethyl acetate (EtOAc) (30 mL) and washed with 2×8 mL of water. After concentration, the crude product is purified by chromatography (heptanes 60%, EtOAc 40%) to give ((S)-1-{6-bromo-1-[5-(4-fluoro-benzoyl)-pyridin-3-ylmethyl]-2-oxo-1,2-dihydro-pyridin-3-ylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester (1D) (95.7 mg, yield 63%) as light yellow solid, MS (ESI) m/e 621.2, 623.3 (M+H+).

Workup

  1. stirringAfter being stirred at room temperature for 5 minutes, to the reaction mixture
  2. stirringThe reaction mixture is stirred at 60□C for 6 hours
  3. washwashed with 2×8 mL of water
  4. concentrationAfter concentration
  5. customthe crude product is purified by chromatography (heptanes 60%, EtOAc 40%)

Sources & evidence

ORD record
ord-39b030a3abd3409c8c42d9c26394ad81
Source dataset
uspto-grants-2011_11
Patent number
US08058272B2

Reaction notes

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