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

HRID 1052462Notes

Reaction equation

HRID 1052462 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][CH:34]=[CH:33][C:32]=2[O:37][CH3:38])=[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:36]=[CH:35][CH:34]=[CH:33][C:32]=2[O:37][CH3:38])=[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 90102281HCID 90102281, compoundHCID 90102580(S)-2-(1-Aminoethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

Product 1

HCID 118433952(S)-4-Amino-N-(2-methoxyphenyl)-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)pyrimidine-5-carboxamideYield 37%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
150 °C

Procedure

(S)-2-(1-Aminoethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (97 mg, 0.36 mmol), 4-amino-6-chloro-N-(2-methoxyphenyl)pyrimidine-5-carboxamide (100 mg, 0.36 mmol), DIEA (400 μl, 2.3 mmol) and cesium fluoride (166 mg, 1.09 mmol) were suspended in tert-butanol (10 ml) and the mixture was heated at 150° C. in a microwave oven for 35 min. 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 flash chromatography using SP1® Purification System (30% to 70%, dichloromethane-ethyl acetate) to obtain 67 mg (37% yield) of the title compound.

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 flash chromatography
  6. customSP1® Purification System (30% to 70%, dichloromethane-ethyl acetate)

Sources & evidence

ORD record
ord-5af5141af7d04b15b4c28b809ccc10e6
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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