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

HRID 1052568Notes

Reaction equation

HRID 1052568 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][O:30][C:31]1[CH:32]=[C:33]([CH:35]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:37]=1)[NH2:34].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:36]1[CH:37]=[C:31]([O:30][CH3:29])[CH:32]=[C:33]([NH2:34])[CH:35]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 901026273-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenamineHCID 118433733HCID 118433733, compound

Product 1

HCID 118433902(S)-2-(1-((6-Amino-5-(3-amino-5-methoxyphenyl)pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-oneYield 53%

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 (150 mg, 0.34 mmol) were added (3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (86 mg, 0.34 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (27 mg, 0.03 mmol) and 340 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 crude was purified by reverse phase using SP1® Purification System to give 87 mg (52% 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 reverse phase
  6. custom® Purification System

Sources & evidence

ORD record
ord-e06af03598ff4bdfb48674eaa8b2541c
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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