Cesium carbonate → (S)-tert-butyl 1-(6-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-2-yloxy)propan-2-ylcarbamate

HRID 1774643Notes

Reaction equation

HRID 1774643 reaction equation
CS([O:5][CH2:6][C@@H:7]([NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH3:8])(=O)=O.[Br:17][C:18]1[CH:19]=[C:20]([NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29](O)[N:28]=2)[C:21](=[O:25])[N:22]([CH3:24])[CH:23]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C(Cl)Cl>[Br:17][C:18]1[CH:19]=[C:20]([NH:26][C:27]2[N:28]=[C:29]([O:5][CH2:6][C@@H:7]([NH:9][C:10](=[O:11])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:8])[CH:30]=[CH:31][CH:32]=2)[C:21](=[O:25])[N:22]([CH3:24])[CH:23]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 10753379(S)-Methanesulphonic acid 2-Boc-aminopropyl esterHCID 178479984HCID 178479984, compound

Product 1

HCID 118117363(S)-tert-butyl 1-(6-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-2-yloxy)propan-2-ylcarbamateYield 22.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 107a (964 mg, 5.5 mmol), 5-Bromo-3-(6-hydroxypyridin-2-ylamino)-1-methylpyridin-2(1H)-one 101a (4 g crude, 16.5 mmol), Cs2CO3 (5.38 g, 11 mmol) in DMF (20 mL) was stirred at 95° C. for 16 h. The reaction mixture was diluted with DCM, washed with water. The organic layer was separated, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography (DCM/MeOH=20/1) to give 107b (550 mg, 22%) as a brown solid. MS-ESI: [M+H]+ 453.1

Workup

  1. washwashed with water
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (DCM/MeOH=20/1)

Sources & evidence

ORD record
ord-9e6e1e265e6e4c939e9abc8f3acd7c39
Source dataset
uspto-grants-2016_02
Patent number
US09260415B2

Reaction notes

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