Potassium Phosphate, Tribasic → HCID 86707190, compound

HRID 539915Notes

Reaction equation

HRID 539915 reaction equation
CC1(C)C(C)(C)OB([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]([C:18]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:10]=2)O1.Cl[C:39]1[N:44]=[C:43]([NH:45][C@H:46]2[CH2:51][CH2:50][CH2:49][C@@H:48]([NH:52][C:53]([C:55]3[N:56]=[CH:57][N:58]([CH3:60])[CH:59]=3)=[O:54])[CH2:47]2)[C:42]([F:61])=[CH:41][N:40]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[F:61][C:42]1[C:43]([NH:45][C@H:46]2[CH2:51][CH2:50][CH2:49][C@@H:48]([NH:52][C:53]([C:55]3[N:56]=[CH:57][N:58]([CH3:60])[CH:59]=3)=[O:54])[CH2:47]2)=[N:44][C:39]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]([C:18]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:10]=2)=[N:40][CH:41]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 667975223-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triphenylmethyl)-1H-pyrazolo[3,4-b]pyridineHCID 86707191HCID 86707191, compound

Product 1

HCID 86707190HCID 86707190, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-pyrazolo[5,4-b]pyridine, 45, (0.259 g, 0.532 mmol) and N-[(1R,3S)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]cyclohexyl]-1-methyl-imidazole-4-carboxamide, 24, (0.150 g, 0.425 mmol) in 2-Me-THF (7.1 mL) and water (1.4 mL) was added K3PO4 (0.316 g, 1.488 mmol). The solution was degassed for 10 minutes under flow of nitrogen. Pd2(dba)3 (0.027 g, 0.030 mmol) and dicyclohexyl-[2-(2,4,6-triisopropylphenyl)-phenyl]phosphane (0.030 g, 0.064 mmol) were added and solution was again degassed under flow of nitrogen. The reaction tube was sealed and heated to 80° C. for 2 hours. The mixture was cooled to room temperature and diluted with water (10 mL). The organic phase was extracted with ethyl acetate, washed with brine (10 mL). The crude was dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (0-7% MeOH [2N NH3] in ethyl acetate) to give the desired compound: LC/MS Gradient 10-90%, 0.1% formic 5 min, C18/ACN, RT=2.78 min (M+H)=678.73.

Workup

  1. customThe solution was degassed for 10 minutes under flow of nitrogen
  2. customsolution was again degassed under flow of nitrogen
  3. customThe reaction tube was sealed
  4. temperatureThe mixture was cooled to room temperature
  5. additiondiluted with water (10 mL)
  6. extractionThe organic phase was extracted with ethyl acetate
  7. washwashed with brine (10 mL)
  8. dry with materialThe crude was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude residue was purified by silica gel chromatography (0-7% MeOH [2N NH3] in ethyl acetate)

Sources & evidence

ORD record
ord-c013c737d9ba4560a047d223d25fddae
Source dataset
uspto-grants-2014_10
Patent number
US08871774B2

Reaction notes

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