Water → 6-(2-fluoro-5-vinylpyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

HRID 1621447Notes

Reaction equation

HRID 1621447 reaction equation
Cl[C:2]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1.[F:18][C:19]1[C:24](B(O)O)=[CH:23][C:22]([CH:28]=[CH2:29])=[CH:21][N:20]=1.C([O-])(=O)C.[K+].O>C(O)C.C(P([Pd](P(C1C=CC(N(C)C)=CC=1)(C(C)(C)C)C(C)(C)C)(Cl)Cl)(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C>[F:18][C:19]1[C:24]([C:2]2[N:10]=[C:9]([CH3:11])[N:8]=[C:7]3[C:3]=2[N:4]=[CH:5][N:6]3[CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)=[CH:23][C:22]([CH:28]=[CH2:29])=[CH:21][N:20]=1

Participants

7

Reactant 4

HCID 962WaterHCID 517044Potassium AcetateHCID 595482686-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 595483472-Fluoro-5-vinylpyridin-3-ylboronic acid

Product 1

HCID 595484346-(2-fluoro-5-vinylpyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Reagents, catalysts & solvents 2

HCID 178482906HCID 178482906, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

6-Chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (984 mg, 3.89 mmol), 2-fluoro-5-vinylpyridin-3-ylboronic acid (882 mg, 5.28 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphino)dichloropalladium (138 mg, 0.195 mmol), and potassium acetate (1.212 g, 12.35 mmol) were suspended in ethanol (12.0 mL) and water (2.4 mL) and the flask was fitted with a reflux condenser and nitrogen was bubbled through the suspension for about 15 seconds. Then, the flask was put in a preheated oil bath (80° C.) and stirred under nitrogen for 1 h. The reaction was cooled to room temperature, diluted with water (20 mL), and extracted with DCM. The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel column (25:1 to 20:1 DCM/2N ammonia in MeOH) to afford 6-(2-fluoro-5-vinylpyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine, which was taken on to the next step. MS (ESI pos. ion) m/z 340 (M+H)+.

Workup

  1. customnitrogen was bubbled through the suspension for about 15 seconds
  2. customThen, the flask was put in a preheated oil bath
  3. temperatureThe reaction was cooled to room temperature
  4. additiondiluted with water (20 mL)
  5. extractionextracted with DCM
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified on a silica gel column (25:1 to 20:1 DCM/2N ammonia in MeOH)

Sources & evidence

ORD record
ord-3669b0edee01487081d4442d20857cba
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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