Potassium Phosphate, Tribasic → HCID 86732436, compound

HRID 1776407Notes

Reaction equation

HRID 1776407 reaction equation
Br[C:2]1[CH:32]=[C:31]([F:33])[C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([C:16]3[N:21]=[C:20]([NH:22][C:23]4[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=4)[C:19]([O:29][CH3:30])=[CH:18][N:17]=3)=[N:8]2)=[C:4]([F:34])[CH:3]=1.[CH:35]1(B(O)O)[CH2:37][CH2:36]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH:35]1([C:2]2[CH:32]=[C:31]([F:33])[C:5]([CH2:6][N:7]3[C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:9]([C:16]4[N:21]=[C:20]([NH:22][C:23]5[CH:24]=[CH:25][N:26]=[CH:27][CH:28]=5)[C:19]([O:29][CH3:30])=[CH:18][N:17]=4)=[N:8]3)=[C:4]([F:34])[CH:3]=2)[CH2:37][CH2:36]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 71553449HCID 71553449, compound

Product 1

HCID 86732436HCID 86732436, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

100 mg of 2-[1-(4-bromo-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine (2-12-1, 0.191 mmol, 1. eq.) were suspended in 3 ml of dry toluene. 21.3 mg of cyclopropylboronic acid (0.248 mmol, 1.3 eq.) 5.36 mg of tricyclohexylphosphane (0.019 mmol, 0.1 eq.), 142 mg of potassium phosphate (0.669 mmol, 3.5 eq.) and 50 μl of water were added. Then 2.15 mg of palladium (II) acetate (0.01 mmol, 0.05 eq.) were added under a nitrogen atmosphere. The mixture was stirred at 100° C. bath temperature for 5 hours. Upon the mixture was cooled to room temperature it was partitioned between water and dichloromethane/isopropanol 4:1. The phases were separated and the aqueous layer was extracted twice with dichloromethane/isopropanol 4:1. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. Preparative HPLC purification provided 28.7 mg (0.06 mmol, 31%) of the analytically pure target compound.

Workup

  1. temperatureUpon the mixture was cooled to room temperature it
  2. customwas partitioned between water and dichloromethane/isopropanol 4:1
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted twice with dichloromethane/isopropanol 4:1
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customPreparative HPLC purification
  8. customprovided 28.7 mg (0.06 mmol, 31%) of the analytically pure target compound

Sources & evidence

ORD record
ord-a4e86d641bb543a2870b55cefaec26bd
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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