Potassium Carbonate → 3-({2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)-pyrimidin-5-yl}oxy)propane-1,2-diol

HRID 1776413Notes

Reaction equation

HRID 1776413 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]2[N:19]=[C:18]([NH:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)[C:17]([OH:27])=[CH:16][N:15]=2)=[N:6]1.Br[CH2:33][CH:34]([OH:37])[CH2:35][OH:36].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]2[N:19]=[C:18]([NH:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)[C:17]([O:27][CH2:33][CH:34]([OH:37])[CH2:35][OH:36])=[CH:16][N:15]=2)=[N:6]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 208273-Bromo-1,2-propanediolHCID 1362713042-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol

Product 1

HCID 867324423-({2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)-pyrimidin-5-yl}oxy)propane-1,2-diol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

25.0 mg of 2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol (3-3, 0.06 mmol, 1 eq.), 28.2 mg of 3-bromo-propane-1,2-diol (0.18 mmol, 3 eq.) and 41.9 mg of potassium carbonate (0.30 mmol, 5 eq.) were suspended in 466 μl of dry DMF. The reaction mixture was stirred at 100° C. oil bath temperature for 18 hours. Then the mixture was partitioned between half saturated aq. sodium chloride solution and ethyl acetate. The phases were separated and the aqueous layer was extracted once more with ethyl acetate and once with dichloromethane/isopropanol 4:1. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The residue was purified by preparative thin layer chromatography to yield 2.60 mg (5.34 μmol, 9%) of the analytically pure target compound.

Workup

  1. customThen the mixture was partitioned between half saturated aq. sodium chloride solution and ethyl acetate
  2. customThe phases were separated
  3. extractionthe aqueous layer was extracted once more with ethyl acetate and once with dichloromethane/isopropanol 4:1
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative thin layer chromatography
  7. customto yield 2.60 mg (5.34 μmol, 9%) of the analytically pure target compound

Sources & evidence

ORD record
ord-78062ced72c342f3b391cc3a8767da93
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

Loading…