Sodium Carbonate → (S)-Methyl 3-(4-amino-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)pyrimidin-5-yl)-5-hydroxybenzoate

HRID 1052357Notes

Reaction equation

HRID 1052357 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1I.[OH:29][C:30]1[CH:31]=[C:32]([CH:37]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:39]=1)[C:33]([O:35][CH3:36])=[O:34].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[NH2:1][C:2]1[C:3]([C:38]2[CH:37]=[C:32]([CH:31]=[C:30]([OH:29])[CH:39]=2)[C:33]([O:35][CH3:36])=[O:34])=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[N:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 10340Sodium Carbonate2×HCID 467396923-Hydroxy-5-(methoxycarbonyl)phenylboronic acid, pinacol esterHCID 118433756(S)-2-(1-((6-Amino-5-iodopyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

Product 1

HCID 131736113(S)-Methyl 3-(4-amino-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)pyrimidin-5-yl)-5-hydroxybenzoateYield 42.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

(S)-2-(1-((6-Amino-5-iodopyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (100 mg, 0.16 mmol) and methyl 3-hydroxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (64 mg, 0.23 mmol) were dissolved in 10 mL dioxane in a microwave vessel. A solution of sodium carbonate (2 M, 365 μl, 0.73 mmol) was added and the mixture was submitted to three vacuum-argon cycles. 2′-(Dimethylamino)-2-biphenylyl-palladium(II) chloride dinorbornylphosphine complex (5 mg, 0.01 mmol) was added and the mixture was submitted to three more vacuum-argon cycles. The reaction mixture was then heated at 120° C. under microwave conditions for 5 h. Further 2′-(dimethylamino)-2-biphenylyl-palladium(II) chloride dinorbornylphosphine complex (5 mg, 0.01 mmol) and sodium carbonate (2 M, 365 μl, 0.73 mmol) were added and the reaction mixture heated at 120° C. under microwave conditions 2 h more. The reaction mixture was cooled at room temperature and partitioned between ethyl acetate and water. The organic phase was washed with water, brine and dried over sodium sulphate, filtered and evaporated under reduced pressure. The residue was purified by reverse phase using SP1® Purification System to obtain 35 mg (42% yield) of the title compound. Purity 100%.

Workup

  1. addition2′-(Dimethylamino)-2-biphenylyl-palladium(II) chloride dinorbornylphosphine complex (5 mg, 0.01 mmol) was added
  2. temperaturethe reaction mixture heated at 120° C. under microwave conditions 2 h more
  3. temperatureThe reaction mixture was cooled at room temperature
  4. custompartitioned between ethyl acetate and water
  5. washThe organic phase was washed with water, brine
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe residue was purified by reverse phase
  10. custom® Purification System

Sources & evidence

ORD record
ord-53544828e69f4988a81f89c34c0805a4
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

Loading…