Sodium Carbonate → ((S)-1-{1-[5-(4-Fluoro-benzoyl)-pyridin-3-ylmethyl]-2-oxo-6-phenyl-1,2-dihydro-pyridin-3-ylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester

HRID 556271Notes

Reaction equation

HRID 556271 reaction equation
[CH2:1]([O:8][C:9](=[O:41])[N:10]([C@H:12]([C:14](=[O:40])[NH:15][C:16]1[C:17](=[O:39])[N:18]([CH2:23][C:24]2[CH:25]=[N:26][CH:27]=[C:28]([C:30](=[O:38])[C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[CH:29]=2)[C:19](Br)=[CH:20][CH:21]=1)[CH3:13])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:42]1(B(O)O)[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:8][C:9](=[O:41])[N:10]([C@H:12]([C:14](=[O:40])[NH:15][C:16]1[C:17](=[O:39])[N:18]([CH2:23][C:24]2[CH:25]=[N:26][CH:27]=[C:28]([C:30](=[O:38])[C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[CH:29]=2)[C:19]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[CH:20][CH:21]=1)[CH3:13])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 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 ester

Product 1

HCID 59200226((S)-1-{1-[5-(4-Fluoro-benzoyl)-pyridin-3-ylmethyl]-2-oxo-6-phenyl-1,2-dihydro-pyridin-3-ylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl esterYield 91%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of ((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) (79 mg, 0.13 mmol) and phenyl boronic acid (19 mg, 0.15 mmol) in 8 mL of toluene, 3 mL of ethanol and Na2CO3 (0.5 mL, 0.5 mmol, 1 M aqueous solution) is degassed under vacuum. PdCl2(PPh3)2 (5 mg, 0.006 mmol) is added to the mixture. The reaction mixture is stirred at 80° C. for 1 hour, cooled to room temperature and diluted with 20 mL of EtOAc. The organic phase is washed with 2×5 mL of water and concentrated. The crude product is purified by chromatography (heptane 60%, EtOAc 40%) to give ((S)-1-{1-[5-(4-fluoro-benzoyl)-pyridin-3-ylmethyl]-2-oxo-6-phenyl-1,2-dihydro-pyridin-3-ylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester (1E) (72 mg, yield 91%) as a light yellow solid. MS (ESI) m/e 619 (M+H+).

Workup

  1. customis degassed under vacuum
  2. temperaturecooled to room temperature
  3. washThe organic phase is washed with 2×5 mL of water
  4. concentrationconcentrated
  5. customThe crude product is purified by chromatography (heptane 60%, EtOAc 40%)

Sources & evidence

ORD record
ord-a1d0034f5fd240aabdb90f6fbd51db6e
Source dataset
uspto-grants-2011_11
Patent number
US08058272B2

Reaction notes

Loading…