Sodium Carbonate → 3-(tert-butyl-5-fluoro-6-(methylthio)pyrimidin-2-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridine

HRID 74958Notes

Reaction equation

HRID 74958 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[C:30]([C:34]1[C:39]([F:40])=[C:38]([S:41][CH3:42])[N:37]=[C:36](Cl)[N:35]=1)([CH3:33])([CH3:32])[CH3:31].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:30]([C:34]1[C:39]([F:40])=[C:38]([S:41][CH3:42])[N:37]=[C:36]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[NH:8][CH:9]=2)[N:35]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 575977475-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 866674234-Tert-butyl-2-chloro-5-fluoro-6-(methylthio)pyrimidine

Product 1

HCID 672859433-(tert-butyl-5-fluoro-6-(methylthio)pyrimidin-2-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridineYield 26.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a degassed solution of 5-chloro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (0.22 g, 0.50 mmol), 4-tert-butyl-2-chloro-5-fluoro-6-thiomethoxypyrimidine, 40a, (0.12 g, 0.50 mmol) in 1,2-dimethoxyethane (3 mL) and aqueous Na2CO3 (0.75 mL of 2 M solution, 1.5 mmol) was added tetrakis(triphenylphosphine)palladium(0) (0.03 g, 0.03 mmol). The reaction mixture was degassed for an additional 15 minutes. The mixture was heated in a microwave at 150° C. for 20 minutes. Ethyl acetate (15 mL) was added. The organic layer was separated and washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The resulting crude residue was purified by silica gel chromatography (0%-100% EtOAc/hexanes) to afford the desired product, 40b (47 mg).

Workup

  1. customThe reaction mixture was degassed for an additional 15 minutes
  2. additionEthyl acetate (15 mL) was added
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting crude residue was purified by silica gel chromatography (0%-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1722b444dbd8459fb68f2fddc5076d5a
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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