Sodium Carbonate → 6-(2-aminopyridin-4-yl)-2,2-dimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

HRID 2364010Notes

Reaction equation

HRID 2364010 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([CH3:13])([CH3:12])[NH:5][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:22]2[CH:27]=[CH:26][N:25]=[C:24]([NH2:28])[CH:23]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[NH2:28][C:24]1[CH:23]=[C:22]([C:2]2[S:10][C:9]3[C:8](=[O:11])[NH:7][C:6]([CH3:13])([CH3:12])[NH:5][C:4]=3[CH:3]=2)[CH:27]=[CH:26][N:25]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 457857074-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 667434256-bromo-2,2-dimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

Product 1

HCID 667434926-(2-aminopyridin-4-yl)-2,2-dimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-bromo-2,2-dimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (0.039 g, 0.15 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (0.022 g, 0.10 mmol), 2 M sodium carbonate (0.075 mL, 0.15 mmol) and 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (0.024 g, 0.030 mmol) in 1,4-dioxane (0.5 mL) was microwave-irradiated at 140° C. for 1 h. Reactions were repeated on 0.10 mmol and 0.20 mmol scales (based on the boronic ester). The reaction mixtures were combined, and concentrated with silica gel (10 mL), and the residue was purified by flash chromatography (silica gel, ethyl acetate to 90:10 ethyl acetate/methanol) to give a crude product as a yellow solid, which was further purified by preparative HPLC. Preparative HPLC was carried out on a Varian Prostar 210 HPLC system using a Phenomenex Luna C18(2) column with UV detection at 254 nm and a solvent gradient of 95:5 solvent A/solvent B to 5:95 solvent A/solvent B (solvent A=water with 0.1% v/v trifluoroacetic acid; solvent B=acetonitrile with 0.1% v/v trifluoroacetic acid). Upon concentration, a TFA salt was obtained, which was dissolved in methanol (10 mL), and the solution was concentrated with NaHCO3 (0.2 g) and silica gel (1 mL). Flash chromatography (silica gel, dichloromethane to 85:15 dichloromethane/methanol) gave the title compound (0.012 g, 11%) as a yellow solid:

Workup

  1. customwas microwave-irradiated at 140° C. for 1 h
  2. customThe reaction mixtures
  3. concentrationconcentrated with silica gel (10 mL)
  4. customthe residue was purified by flash chromatography (silica gel, ethyl acetate to 90:10 ethyl acetate/methanol)
  5. customto give a crude product as a yellow solid, which
  6. customwas further purified by preparative HPLC
  7. concentrationUpon concentration

Sources & evidence

ORD record
ord-33b8e708f69646cbac94ffeb8537044b
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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