Water → [4-(5-Amino-2-pyridin-3-yl-pyrimidin-4-yloxy)-phenyl]-carbamic acid benzyl ester

HRID 1894156Notes

Reaction equation

HRID 1894156 reaction equation
[CH2:1]([O:8][C:9](=[O:26])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]2[C:23]([NH2:24])=[CH:22][N:21]=[C:20](Cl)[N:19]=2)=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:27]1[CH:32]=[CH:31][CH:30]=[C:29](B(O)O)[CH:28]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>O1CCOCC1.CCO.CCOC(C)=O.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[CH2:1]([O:8][C:9](=[O:26])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]2[C:23]([NH2:24])=[CH:22][N:21]=[C:20]([C:29]3[CH:28]=[N:27][CH:32]=[CH:31][CH:30]=3)[N:19]=2)=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27343783-Pyridinylboronic acidHCID 58247429HCID 58247429, compound

Product 1

HCID 58247431[4-(5-Amino-2-pyridin-3-yl-pyrimidin-4-yloxy)-phenyl]-carbamic acid benzyl esterYield 64.5%

Reagents, catalysts & solvents 4

HCID 178477754HCID 178477754, compoundCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a teflon-lined septum sealed Schlenk tube, a mixture of Compound 11a (1.0 g; 2.7 mmol), pyridin-3-yl boronic acid (0.83 g; 6.75 mmol), Cs2CO3 (2.60 g; 8.1 mmol) and [1,1-Bis(diphenylphosphino)-ferrocene]dichloro-palladium(11) (0.49 g; 0.6 mmol) in a mixture of dioxane (15 mL) and EtOH (1 mL) was irradiated in a microwave reactor at 150° C. for 55 min. The reaction mixture was poured into water, diluted with EtOAc and the solid was collected by filtration. The organic phase was isolated and dried over MgSO4. and the reaction mixture was concentrated under reduced pressure. The resultant residue was purified by reverse phase HPLC, eluting with a CH3CN—H2O (0.5% TFA) gradient to afford Compound 11b (0.72 g; 42% yield based on di-TFA). 1H-NMR (300 MHz, MeOH-d4): δ 9.2 (s, 1H), 8.9 (d, 1H), 8.7 (d, 1H), 8.2 (s, 1H), 8.0 (m, 1H), 7.5 (d, 2H), 7.5-7.3 (m, 6H), 7.2 (m, 2H), 5.2 (s, 2H); MS: m/z 414.2 (M+H)+.

Workup

  1. customsealed Schlenk tube
  2. customwas irradiated in a microwave reactor at 150° C. for 55 min
  3. filtrationthe solid was collected by filtration
  4. customThe organic phase was isolated
  5. dry with materialdried over MgSO4
  6. concentrationand the reaction mixture was concentrated under reduced pressure
  7. customThe resultant residue was purified by reverse phase HPLC
  8. washeluting with a CH3CN—H2O (0.5% TFA) gradient

Sources & evidence

ORD record
ord-f846ffb215db4fd384f451a553248648
Source dataset
uspto-grants-2013_08
Patent number
US08513271B2

Reaction notes

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