Ethanol → tert-butyl 4-((6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)methyl)piperazine-1-carboxylate

HRID 1621463Notes

Reaction equation

HRID 1621463 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[C:17](B(O)O)[C:18]([F:21])=[N:19][CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:26]1[N:34]=[C:33]([CH3:35])[N:32]=[C:31]2[C:27]=1[N:28]=[CH:29][N:30]2[CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][O:37]1.C([O-])(=O)C.[K+].C(O)C.O>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:21][C:18]1[N:19]=[CH:20][C:15]([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)=[CH:16][C:17]=1[C:26]1[N:34]=[C:33]([CH3:35])[N:32]=[C:31]2[C:27]=1[N:28]=[CH:29][N:30]2[CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][O:37]1

Participants

7

Reactant 5

HCID 702EthanolHCID 962WaterHCID 517044Potassium AcetateHCID 59548218(5-((4-(tert-Butoxycarbonyl)piperazin-1-yl)methyl)-2-fluoropyridin-3-yl)boronic acidHCID 595482686-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 59548429tert-butyl 4-((6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)methyl)piperazine-1-carboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)Catalyst

Conditions

Temperature
80 °C

Procedure

A mixture of 5-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)-2-fluoropyridin-3-ylboronic acid (655 mg, 1.931 mmol), 6-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (586 mg, 2.317 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Aldrich) (25.6 mg, 0.097 mmol) and potassium acetate (285 mg, 4.83 mmol) in ethanol (6.00 mL, 103 mmol) and H2O (1.00 mL, 55.5 mmol) was heated at 80° C. for 2 h. After cooling, the reaction mixture was concentrated and the crude product was adsorbed onto a plug of silica gel and chromatographed through a RediSep®, Teledyne ISCO, Lincoln, Nebr., pre-packed silica gel column (pure hexanes to 50% ethyl acetate in hexane) to give the tert-butyl 4-((6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)methyl)piperazine-1-carboxylate as a pale yellow foam (0.877 g, 89%). LCMS (API-ES) m/z 512 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated
  3. customchromatographed through a RediSep®, Teledyne ISCO, Lincoln, Nebr

Sources & evidence

ORD record
ord-3c3739bcf0484654b4361e56c004d027
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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