Potassium Phosphate, Tribasic → 5-chloro-3-(5-fluoro-4-(methylthio)pyrimidin-2-yl)-1-trityl-1H-pyrazolo[3,4-b]pyridine

HRID 539925Notes

Reaction equation

HRID 539925 reaction equation
Cl[C:2]1[N:7]=[C:6]([S:8][CH3:9])[C:5]([F:10])=[CH:4][N:3]=1.[Cl:11][C:12]1[CH:13]=[C:14]2[C:20](B3OC(C)(C)C(C)(C)O3)=[N:19][N:18]([C:30]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:15]2=[N:16][CH:17]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O.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]>[Cl:11][C:12]1[CH:13]=[C:14]2[C:20]([C:2]3[N:7]=[C:6]([S:8][CH3:9])[C:5]([F:10])=[CH:4][N:3]=3)=[N:19][N:18]([C:30]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)([C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[C:15]2=[N:16][CH:17]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 136082512-Chloro-5-fluoro-4-(methylsulfanyl)pyrimidineHCID 679756635-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 679766315-chloro-3-(5-fluoro-4-(methylthio)pyrimidin-2-yl)-1-trityl-1H-pyrazolo[3,4-b]pyridine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×

Conditions

Temperature
125 °C

Procedure

A mixture of 2-chloro-5-fluoro-4-methylsulfanyl-pyrimidine (0.26 g, 1.44 mmol) and 5-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-pyrazolo[3,4-b]pyridine, 33, (0.75 g, 1.44 mmol) and K3PO4 (0.96 g, 4.53 mmol) in water (1.5 mL) and 2-Me-THF (7.5 mL) was degassed with nitrogen bubbling for 15 min. Then, X-Phos (0.07 g, 0.14 mmol) and Pd2(dba)3 (0.03 g, 0.04 mmol) was added and the vessel was sealed and heated to 125° C. with microwave irradiation for 30 min. After cooling to room temperature, water was added and the mixture was extracted and with ether and 2-Me-THF. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. Flash chromatography (SiO2, 0-100% EtOAc-hexanes, gradient elution) provided 230 mg of the desired product which was used without further purification: LC/MS Gradient 10-90%, 0.1% formic 5 min, C18/ACN, RT=3.46 min (M+H) 538.01.

Workup

  1. customwas degassed with nitrogen bubbling for 15 min
  2. customthe vessel was sealed
  3. temperatureAfter cooling to room temperature
  4. extractionthe mixture was extracted and with ether and 2-Me-THF
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. washFlash chromatography (SiO2, 0-100% EtOAc-hexanes, gradient elution)

Sources & evidence

ORD record
ord-38be78d9a92b4c28b2fc44bd9fa059c3
Source dataset
uspto-grants-2014_10
Patent number
US08871774B2

Reaction notes

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