Cesium carbonate → (S)-2-(1-((6-Amino-5-(3-(difluoromethyl)-5-hydroxyphenyl)pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

HRID 1052771Notes

Reaction equation

HRID 1052771 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]=1Br.[F:29][CH:30]([F:47])[C:31]1[CH:32]=[C:33]([OH:46])[CH:34]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:36]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C>[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]=1[C:35]1[CH:34]=[C:33]([OH:46])[CH:32]=[C:31]([CH:30]([F:47])[F:29])[CH:36]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 901024333-(Difluoromethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 118433733HCID 118433733, compound

Product 1

HCID 118433876(S)-2-(1-((6-Amino-5-(3-(difluoromethyl)-5-hydroxyphenyl)pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-oneYield 64%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-2-(1-((6-amino-5-bromopyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (65 mg, 0.15 mmol) were added 3-(difluoromethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (91 mg, 0.15 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (12 mg, 0.01 mmol) and 147 μl of a 2M aqueous solution of cesium carbonate in dioxane (2 ml). The mixture was stirred under argon atmosphere at 100° C. for 18 hours and then diluted with ethyl acetate. The resulting solution was washed with water and brine, dried over magnesium sulphate, filtered and the solvents were removed under reduced pressure. The product was purified by reverse phase using SP1® Purification System to give 48 mg (64% yield) as a solid. Purity 99%.

Workup

  1. washThe resulting solution was washed with water and brine
  2. dry with materialdried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvents were removed under reduced pressure
  5. customThe product was purified by reverse phase
  6. custom® Purification System
  7. customto give 48 mg (64% yield) as a solid

Sources & evidence

ORD record
ord-da3687c8e80f469fbd09aeb3eeee4c77
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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