Cesium fluoride → (S)-4-Amino-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)-N-(4-(N-methylsulfamoyl)phenyl)pyrimidine-5-carboxamide

HRID 1052837Notes

Reaction equation

HRID 1052837 reaction equation
[NH2:1][C@H:2]([C:4]1[N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:8](=[O:16])[C:7]2=[C:17]([CH3:20])[CH:18]=[CH:19][N:6]2[N:5]=1)[CH3:3].[NH2:21][C:22]1[C:27]([C:28]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([S:37](=[O:41])(=[O:40])[NH:38][CH3:39])=[CH:33][CH:32]=2)=[O:29])=[C:26](Cl)[N:25]=[CH:24][N:23]=1.CCN(C(C)C)C(C)C.[F-].[Cs+]>C(O)(C)(C)C>[NH2:21][C:22]1[C:27]([C:28]([NH:30][C:31]2[CH:32]=[CH:33][C:34]([S:37](=[O:41])(=[O:40])[NH:38][CH3:39])=[CH:35][CH:36]=2)=[O:29])=[C:26]([NH:1][C@H:2]([C:4]2[N:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:8](=[O:16])[C:7]3=[C:17]([CH3:20])[CH:18]=[CH:19][N:6]3[N:5]=2)[CH3:3])[N:25]=[CH:24][N:23]=1

Participants

6

Reactant 4

HCID 25953Cesium fluorideHCID 81531DiisopropylethylamineHCID 90102580(S)-2-(1-Aminoethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-oneHCID 118433761HCID 118433761, compound

Product 1

HCID 118433741(S)-4-Amino-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)-N-(4-(N-methylsulfamoyl)phenyl)pyrimidine-5-carboxamideYield 23%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

(S)-2-(1-Aminoethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (100 mg, 0.33 mmol), 4-amino-6-chloro-N-(4-(N-methylsulfamoyl)phenyl)pyrimidine-5-carboxamide (123 mg, 0.36 mmol), DIEA (344 μl, 1.97 mmol) and cesium fluoride (150 mg, 0.99 mmol) were suspended in tert-butanol (10 ml) and the mixture was heated at 80° C. in a sealed tube for 24 h. The solvent was evaporated under reduced pressure and the reaction mixture was diluted with ethyl acetate and washed with saturated ammonium chloride solution and brine. After evaporation of the solvent, the residue was purified by reverse phase chromatography using SP1® Purification System to give 47 mg (23% yield) as a solid. Purity 94%.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. additionthe reaction mixture was diluted with ethyl acetate
  3. washwashed with saturated ammonium chloride solution and brine
  4. customAfter evaporation of the solvent
  5. customthe residue was purified by reverse phase chromatography
  6. customSP1® Purification System
  7. customto give 47 mg (23% yield) as a solid

Sources & evidence

ORD record
ord-0730ddda68f4452ab2b5175793ec6bdc
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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