Sodium Carbonate → HCID 136339761, compound

HRID 2389030Notes

Reaction equation

HRID 2389030 reaction equation
I[N:2]1[C:6]2[N:7]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=3)[CH2:9][NH:10][C:5]=2[CH:4]=[CH:3]1.[CH3:18][O:19][C:20]1[CH:21]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:23]=[CH:24][C:25]=1[O:26]CC1C=CC(OC)=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.ClCCl.C(#N)C>[CH3:18][O:19][C:20]1[CH:21]=[C:22]([N:2]2[C:6]3[N:7]=[C:8]([C:11]4[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=4)[CH2:9][NH:10][C:5]=3[CH:4]=[CH:3]2)[CH:23]=[CH:24][C:25]=1[OH:26]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 670612332-[3-Methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 136405680HCID 136405680, compound

Product 1

HCID 136339761HCID 136339761, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 178418903HCID 178418903, compoundCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

84 mg (0.25 mmol) of 4-(5-iodo-1H-pyrrolo[2,3-b]pyrazin-3-yl)-phenol, 120 mg (0.33 mmol) of 2-[3-methoxy-4-(4-methoxy-benzyloxy)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane and 15 mg (8 mol %) of dichlorobis(triphenylphosphino)palladium(II) were placed in a vial and 1.5 ml of acetonitrile and 1.5 ml of a 2 M aqueous solution of sodium carbonate were added. The mixture was irradiated in a Personal Chemistry® microwave reactor to 165° C. for 1200 sec. The resulting mixture was distributed between dichloromethane and a saturated aqueous solution of sodium bicarbonate. The aqueous layer was extracted twice with dichloromethane and the combined organic phases were dried over sodium sulfate and evaporated. The crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes. The resulting intermediate was dissolved in 120 ml of dichloromethane and 1.5 g (2.12 mmol) of PS-thiophenol (Argonaut Technologies) was added. To this was added 2 ml of trifluoroacetic acid and the mixture stirred at room temperature for 1 hour. The resin was filtered off and washed with dichloromethane. The filtrate was washed with a saturated aqueous solution of sodium bicarbonate. The phases were separated and the aqueous layer extracted twice with ethyl acetate. All organic phases were combined, dried over sodium sulfate and evaporated. The residue was heated up with acetonitrile, cooled down to room temperature and the supernatant was removed. The residue was dried in vacuo to afford 15 mg (45 μmol, 18% yield) of 4-{5-[3-methoxy-4-hydroxyphenyl]-1H-pyrrolo[2,3-b]pyrazin-3-yl}-phenol as a beige powder. 1H-NMR (d6-DMSO) δ: 12.06 [1H] d, 9.35 [1H] s, 9.30 [1H] s, 8.83 [1H] s, 8.20 [1H] d, 8.12 [2H] d(m), 7.75 [1H] d, 7.65 [1H] dd, 6.93 [1H] d, 6.85 [2H] d(m), 3.91 [3H] s. MS, m/z: 334 [MH+].

Workup

  1. additionwere added
  2. customThe mixture was irradiated in a Personal Chemistry® microwave reactor to 165° C. for 1200 sec
  3. extractionThe aqueous layer was extracted twice with dichloromethane
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. customevaporated
  6. customThe crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes
  7. dissolutionThe resulting intermediate was dissolved in 120 ml of dichloromethane
  8. addition1.5 g (2.12 mmol) of PS-thiophenol (Argonaut Technologies) was added
  9. additionTo this was added 2 ml of trifluoroacetic acid
  10. filtrationThe resin was filtered off
  11. washwashed with dichloromethane
  12. washThe filtrate was washed with a saturated aqueous solution of sodium bicarbonate
  13. customThe phases were separated
  14. extractionthe aqueous layer extracted twice with ethyl acetate
  15. dry with materialdried over sodium sulfate
  16. customevaporated
  17. temperatureThe residue was heated up with acetonitrile
  18. temperaturecooled down to room temperature
  19. customthe supernatant was removed
  20. customThe residue was dried in vacuo

Sources & evidence

ORD record
ord-e2de856bb91746c79b006d8b9586bdc9
Source dataset
uspto-grants-2012_09
Patent number
US08268994B2

Reaction notes

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