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

HRID 2171900Notes

Reaction equation

HRID 2171900 reaction equation
Cl[C:2]1[N:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][N:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[F:18][C:19]1[CH:20]=[C:21]2[C:27](B3OC(C)(C)C(C)(C)O3)=[N:26][N:25]([C:37]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:22]2=[N:23][CH:24]=1>O.CC1CCCO1.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]>[F:18][C:19]1[CH:20]=[C:21]2[C:27]([C:2]3[N:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][N:3]=3)=[N:26][N:25]([C:37]([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)([C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)[C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:22]2=[N:23][CH:24]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 164271482-Chloro-4-(methylthio)pyrimidineHCID 679757175-Fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-pyrazolo[3,4-b]pyridine2×

Product 1

HCID 712479685-fluoro-3-(4-(methylthio)pyrimidin-2-yl)-1-trityl-1H-pyrazolo[3,4-b]pyridine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
95 °C

Procedure

A solution of 2-chloro-4-methylsulfanyl-pyrimidine (0.25 g, 1.56 mmol), K3PO4 (0.99 g, 4.67 mmol) and 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-pyrazolo[3,4-b]pyridine, 135a, (0.87 g, 1.71 mmol) in water (1 mL) and 2-methyltetrahydrofuran (9 mL) was degassed under a stream of nitrogen for 15 minutes. Then, Pd2(dba)3 (0.04 g, 0.05 mmol) was added and the mixture was degassed for an additional 2-3 minutes. The vessel was sealed and heated to 95° C. overnight. After separating the layers, the organic phase was washed with water. The resulting solid was filtered and washed with ether and MeTHF. Filtered through PSA cartridge with MeOH/dichloromethane mixture to give the desired product as a white solid: LCMS Gradient 60-98%, 0.1% formic acid, 7 min, C4/ACN, Retention Time=2.68 min (M+Na) 526.1.

Workup

  1. customthe mixture was degassed for an additional 2-3 minutes
  2. customThe vessel was sealed
  3. customAfter separating the layers
  4. washthe organic phase was washed with water
  5. filtrationThe resulting solid was filtered
  6. washwashed with ether and MeTHF
  7. filtrationFiltered through PSA cartridge with MeOH/dichloromethane mixture

Sources & evidence

ORD record
ord-5f432812757b4d90aa90fe7ae1da9e10
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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