Cesium carbonate → ethyl 6-(6-(3-ethylureido)-4-(4-(1-methyl-1H-pyrazol-4-yl)thiazol-2-yl)pyridin-3-yl)-1-((1-methyl-1H-imidazol-4-yl)methyl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate

HRID 1047179Notes

Reaction equation

HRID 1047179 reaction equation
[CH2:1]([NH:3][C:4](=[O:26])[NH:5][C:6]1[N:11]=[CH:10][C:9](B(O)O)=[C:8]([C:15]2[S:16][CH:17]=[C:18]([C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)[N:19]=2)[CH:7]=1)[CH3:2].Br[C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][N:37]=1)[N:34]([CH2:38][C:39]1[N:40]=[CH:41][N:42]([CH3:44])[CH:43]=1)[CH:33]=[C:32]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[C:31]2=[O:50].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([NH:3][C:4](=[O:26])[NH:5][C:6]1[N:11]=[CH:10][C:9]([C:28]2[CH:29]=[C:30]3[C:35](=[CH:36][N:37]=2)[N:34]([CH2:38][C:39]2[N:40]=[CH:41][N:42]([CH3:44])[CH:43]=2)[CH:33]=[C:32]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[C:31]3=[O:50])=[C:8]([C:15]2[S:16][CH:17]=[C:18]([C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)[N:19]=2)[CH:7]=1)[CH3:2]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 672880116-(3-Ethylureido)-4-(4-(1-methyl-1h-pyrazol-4-yl)thiazol-2-yl)pyridin-3-ylboronic acid2×HCID 86665055ethyl 6-bromo-1-((1-methyl-1H-imidazol-4-yl)methyl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate2×

Product 1

HCID 68749575ethyl 6-(6-(3-ethylureido)-4-(4-(1-methyl-1H-pyrazol-4-yl)thiazol-2-yl)pyridin-3-yl)-1-((1-methyl-1H-imidazol-4-yl)methyl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylateYield 26.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

In a microwave vessel, 6-(3-ethylureido)-4-(4-(1-methyl-1H-pyrazol-4-yl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 98, 0.2 g, 0.54 mmol), ethyl 6-bromo-1-((1-methyl-1H-imidazol-4-yl)methyl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate (Intermediate 102, 0.21 g, 0.54 mmol) and cesium carbonate (0.229 g, 0.70 mmol) were combined and suspended in a mixture of dioxane and water (5:1; 2.5 mL/0.5 mL). The suspension was degassed and purged with nitrogen. Pd(PPh3)4 (0.05 g, 0.04 mmol) was added and the mixture was degassed and purged a second time. The reaction mixture was heated in the microwave at 90° C. for 90 minutes. The reaction was partitioned between water and ethyl acetate, the layers were separated, and the organic phase was washed with saturated NaHCO3, water and brine, then dried over magnesium sulfate, and concentrated. The resulting solids were filtered, washed with acetonitrile followed by chloroform. Isolation gave 90 mg of the title compound as an off-white solid.

Workup

  1. customThe suspension was degassed
  2. custompurged with nitrogen
  3. customthe mixture was degassed
  4. custompurged a second time
  5. customThe reaction was partitioned between water and ethyl acetate
  6. customthe layers were separated
  7. washthe organic phase was washed with saturated NaHCO3, water and brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. filtrationThe resulting solids were filtered
  11. washwashed with acetonitrile

Sources & evidence

ORD record
ord-f09193da7c054338baa9b45faa7ca189
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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