Potassium Carbonate → HCID 67198434, compound

HRID 1948738Notes

Reaction equation

HRID 1948738 reaction equation
Cl[C:2]1[C:11]([CH2:12]O)=[CH:10][C:9]2[C:4](=[C:5]([CH3:14])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[F:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.C([O-])([O-])=O.[K+].[K+].P(Br)(Br)Br.[SH:35][C:36]1[N:44]=[CH:43][N:42]=[C:41]2[C:37]=1[NH:38][CH:39]=[N:40]2>COCCOC.O.C(Cl)Cl.CN(C=O)C.CCOC(C)=O.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>[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:2]2[C:11]([CH2:12][S:35][C:36]3[N:44]=[CH:43][N:42]=[C:41]4[C:37]=3[NH:38][CH:39]=[N:40]4)=[CH:10][C:9]3[C:4](=[C:5]([CH3:14])[CH:6]=[CH:7][CH:8]=3)[N:3]=2)=[CH:18][CH:17]=1

Participants

12

Reactant 5

HCID 11430Potassium Carbonate2×HCID 24614Phosphorus tribromideHCID 2856454-Fluorophenylboronic acidHCID 865104(2-Chloro-8-methylquinolin-3-yl)methanolHCID 178527888HCID 178527888, compound

Product 1

HCID 67198434HCID 67198434, compoundYield 45%

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (2-chloro-8-methylquinolin-3-yl)methanol (250 mg, 1.21 mmol) in DME (4 mL) and water (0.4 mL) was added 4-fluorophenylboronic acid (203 mg, 1.45 mmol) and K2CO3 (250 mg, 1.81 mmol). The mixture was degassed by bubbling through N2 for 5 minutes before adding Pd(PPh3)4 (70 mg, 0.06 mmol) and degassing for a further 5 minutes. The reaction mixture was heated to 120° C. under microwave irradiation for 1 h. The mixture was diluted with EtOAc (100 mL) and washed with water (30 mL). The organic layer was separated, dried (MgSO4) and concentrated in vacuo. Purification by column chromatography (SiO2, 0-50% EtOAc in heptane) gave a white solid. To a solution of this solid (230 mg) in DCM (10 mL) was added phosphorus tribromide (0.4 mL, 4.31 mmol) and the mixture was stirred at r.t. for 90 minutes. The mixture was partitioned between DCM (100 mL) and 10% aqueous K2CO3 solution (30 mL). The organic layer was separated, dried (MgSO4) and the solvent removed in vacuo to give a white solid. To a solution of this solid in DMF (30 mL) was added potassium carbonate (352 mg, 2.55 mmol) and 6-mercaptopurine (433 mg, 2.55 mmol). The reaction mixture was stirred at r.t. for 18 h. The mixture was diluted with EtOAc (100 mL) and washed with water (7×40 mL). The organic layer was separated, dried (MgSO4) and the solvent removed in vacuo to give the title compound (217 mg, 45%) as a white solid. δH (DMSO-d6) 13.54 (br s, 1H), 8.63 (s, 1H), 8.57 (s, 1H), 8.42 (s, 1H), 7.75-7.83 (m, 3H), 7.60-7.65 (m, 1H), 7.45-7.55 (m, 1H), 7.30-7.38 (m, 2H), 4.85 (s, 2H), 2.69 (s, 3H). LCMS (ES+) 402.2 (M+H)+, RT 3.79 minutes (Method 3).

Workup

  1. customThe mixture was degassed
  2. customby bubbling through N2 for 5 minutes
  3. customdegassing for a further 5 minutes
  4. additionThe mixture was diluted with EtOAc (100 mL)
  5. washwashed with water (30 mL)
  6. customThe organic layer was separated
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography (SiO2, 0-50% EtOAc in heptane)
  10. customgave a white solid
  11. customThe mixture was partitioned between DCM (100 mL) and 10% aqueous K2CO3 solution (30 mL)
  12. customThe organic layer was separated
  13. dry with materialdried (MgSO4)
  14. customthe solvent removed in vacuo
  15. customto give a white solid
  16. stirringThe reaction mixture was stirred at r.t. for 18 h
  17. washwashed with water (7×40 mL)
  18. customThe organic layer was separated
  19. dry with materialdried (MgSO4)
  20. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-70ca3af9ed224afc8b70c11cd876a4a5
Source dataset
uspto-grants-2013_03
Patent number
US08399483B2

Reaction notes

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