Cesium carbonate → 1-(2-(2-(5-Chloro-2-(pyrimidin-5-ylamino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592385Notes

Reaction equation

HRID 592385 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([Cl:22])=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[NH2:29][C:30]1[CH:31]=[N:32][CH:33]=[N:34][CH:35]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[Cl:22][C:5]1[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)=[N:7][C:2]([NH:29][C:30]2[CH:31]=[N:32][CH:33]=[N:34][CH:35]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 344373Pyrimidin-5-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867122951-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 732965741-(2-(2-(5-Chloro-2-(pyrimidin-5-ylamino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamideYield 21%

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A suspension of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A14 (0.100 g, 0.297 mmol), Cs2CO3 (0.291 g, 0.892 mmol) and 5-aminopyrimidine (56.6 mg, 0.595 mmol) in 1,4-dioxane (3 mL) was sonicated for 10 minutes. Xantphos (6.9 mg, 12 μmol) and Pd(II) acetate (1.3 mg, 5.9 μmol) were added and the reaction was irradiated in the microwave at 120° C. for 20 minutes. The resulting mixture was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. then 0-40% MeOH in EtOAc) to give a solid which was suspended in 0.5 M aqueous citric acid (50 mL) and sonicated for 10 minutes. The precipitate was collected by filtration and the filter cake was washed with 2 M aqueous NaOH (100 mL), cyclohexane (100 mL) and air dried to give the title compound 12 as a yellow solid (25 mg, 21%). LCMS-B: rt 4.89 min; m/z 395.0 [M+H]+.

Workup

  1. customwas sonicated for 10 minutes
  2. customthe reaction was irradiated in the microwave at 120° C. for 20 minutes
  3. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.
  4. custom0-40% MeOH in EtOAc) to give a solid which
  5. customsonicated for 10 minutes
  6. filtrationThe precipitate was collected by filtration
  7. washthe filter cake was washed with 2 M aqueous NaOH (100 mL), cyclohexane (100 mL) and air
  8. customdried

Sources & evidence

ORD record
ord-a2b5d97d297a4967bdcb3572b66cc433
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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