Cesium fluoride → (S)-4-Amino-N-(3-methoxy-5-(methylsulfonamido)phenyl)-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 1052851Notes

Reaction equation

HRID 1052851 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]=[C:35]([NH:37][S:38]([CH3:41])(=[O:40])=[O:39])[CH:34]=[C:33]([O:42][CH3:43])[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:36]=[C:35]([NH:37][S:38]([CH3:41])(=[O:39])=[O:40])[CH:34]=[C:33]([O:42][CH3:43])[CH:32]=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 90103324HCID 90103324, compound

Product 1

HCID 90102993(S)-4-Amino-N-(3-methoxy-5-(methylsulfonamido)phenyl)-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 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 (117 mg, 0.38 mmol), 4-amino-6-chloro-N-(3-methoxy-5-(methylsulfonamido)phenyl)pyrimidine-5-carboxamide (266 mg, 65% purity, 0.46 mmol), DIEA (404 μl, 2.32 mmol) and cesium fluoride (175 mg, 1.14 mmol) were suspended in tert-butanol (12 ml) and the mixture was heated at 80° C. in a sealed tube for 3 days. 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 using SP1® Purification System to give 54 mg (23% yield) as a solid. Purity 97%.

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
  6. custom® Purification System
  7. customto give 54 mg (23% yield) as a solid

Sources & evidence

ORD record
ord-ff5b7d35709d4a719a6edf5149050e82
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

Loading…