Cesium fluoride → HCID 118433935, compound

HRID 1052459Notes

Reaction equation

HRID 1052459 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][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=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][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=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 901029134-Amino-6-chloro-N-(3-methoxybenzyl)pyrimidine-5-carboxamide

Product 1

HCID 118433935HCID 118433935, compoundYield 59.4%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

(S)-2-(1-Aminoethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (92 mg, 0.34 mmol), 4-amino-6-chloro-N-(3-methoxybenzyl)pyrimidine-5-carboxamide (100 mg, 0.34 mmol), DIEA (360 μl, 2.07 mmol) and cesium fluoride (157 mg, 1.03 mmol) were suspended in tert-butanol (10 ml) and the mixture was heated to reflux for 48 h. The solvent was evaporated under reduced pressure and the crude 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 (0% to 40%, dichloromethane-ethyl acetate) to obtain 106 mg (59% yield) of the title compound.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 48 h
  3. customThe solvent was evaporated under reduced pressure
  4. additionthe crude was diluted with ethyl acetate
  5. washwashed with saturated ammonium chloride solution and brine
  6. customAfter evaporation of the solvent
  7. customthe residue was purified by flash chromatography
  8. customSP1® Purification System (0% to 40%, dichloromethane-ethyl acetate)

Sources & evidence

ORD record
ord-5373aab141aa44f3bb9132aaa592312a
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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