Cesium carbonate → (S)-N-(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-(trifluoromethyl)phenyl)methanesulfonamide

HRID 1052854Notes

Reaction equation

HRID 1052854 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.[CH3:29][S:30]([NH:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)(=[O:32])=[O:31].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C>[NH2:1][C:2]1[C:3]([C:36]2[CH:35]=[C:34]([NH:33][S:30]([CH3:29])(=[O:31])=[O:32])[CH:39]=[C:38]([C:40]([F:42])([F:43])[F:41])[CH:37]=2)=[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

6

Reactant 3

HCID 10796Cesium carbonateHCID 90102216(3-(Methylsulfonamido)-5-(trifluoromethyl)phenyl)boronic acidHCID 118433733HCID 118433733, compound

Product 1

HCID 118433879(S)-N-(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-(trifluoromethyl)phenyl)methanesulfonamideYield 38%

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 (100 mg, 0.23 mmol) were added (3-(methylsulfonamido)-5-(trifluoromethyl)phenyl)boronic acid (529 mg, 24% purity, 0.45 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (19 mg, 0.02 mmol) and 284 μl of a 2M aqueous solution of cesium carbonate in dioxane (3 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 crude was purified by flash chromatography (0 to 80%, hexane-ethyl acetate) using SP1® Purification System to give 52 mg (38% yield) of the title compound as a white solid. Purity 98%.

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 crude was purified by flash chromatography (0 to 80%, hexane-ethyl acetate)
  6. customSP1® Purification System

Sources & evidence

ORD record
ord-3984437d1d2f42c289590eb711752b69
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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