Potassium Carbonate → HCID 44126369, compound

HRID 1948737Notes

Reaction equation

HRID 1948737 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.[N:15]1[CH:20]=[CH:19][CH:18]=[C:17](B(O)O)[CH:16]=1.C([O-])([O-])=O.[K+].[K+].P(Br)(Br)Br.[SH:34][C:35]1[N:43]=[CH:42][N:41]=[C:40]2[C:36]=1[NH:37][CH:38]=[N:39]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>[CH3:14][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([C:17]1[CH:16]=[N:15][CH:20]=[CH:19][CH:18]=1)[C:11]([CH2:12][S:34][C:35]1[N:43]=[CH:42][N:41]=[C:40]3[C:36]=1[NH:37][CH:38]=[N:39]3)=[CH:10]2

Participants

12

Reactant 5

HCID 11430Potassium Carbonate2×HCID 24614Phosphorus tribromideHCID 865104(2-Chloro-8-methylquinolin-3-yl)methanolHCID 27343783-Pyridinylboronic acidHCID 178527888HCID 178527888, compound

Product 1

HCID 44126369HCID 44126369, compoundYield 27.7%

Reagents, catalysts & solvents 6

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

Conditions

Temperature
120 °C

Procedure

A mixture of (2-chloro-8-methylquinolin-3-yl)methanol (250 mg, 1.21 mmol), pyridine-3-boronic acid (178 mg, 1.45 mmol) and K2CO3 (250 mg, 1.81 mmol) in DME (4 mL) and water (0.4 mL) was degassed for 5 minutes. Pd(PPh3)4 (70 mg, 0.06 mmol) was added and the reaction mixture was degassed for a further 5 minutes and heated to 120° C. under microwave irradiation for 1 h. The solvent was removed in vacuo and the product obtained was dissolved in DCM (19 mL). Phosphorus tribromide (0.83 mL, 8.8 mmol) was added to the mixture, which was stirred at r.t. for 90 minutes. The mixture was partitioned between DCM (50 mL) and 10% aqueous K2CO3 solution (30 mL). The organic layer was dried (MgSO4) and the solvent removed in vacuo. The product obtained was dissolved in DMF (5 mL) and to the mixture was added K2CO3 (64 mg, 0.46 mmol) and 6-mercaptopurine (78 mg, 0.46 mmol). After stirring at r.t. for 18 h, the reaction mixture was diluted with EtOAc (150 mL) and washed with water (7×50 mL). The organic layer was separated, dried (MgSO4), filtered and the solvent removed in vacuo. Purification by column chromatography (SiO2, 1-10% MeOH in DCM) gave the title compound (49 mg, 10%) as an off-white solid. δH (DMSO-d6) 13.51 (br s, 1H), 8.92-8.94 (m, 1H), 8.62-8.65 (m, 1H), 8.61 (s, 1H), 8.58 (s, 1H), 8.40 (s, 1H), 8.18 (d, J 7.7 Hz, 1H), 7.85 (d, J 7.7 Hz, 1H), 7.50-7.66 (m, 3H), 4.86 (s, 2H), 2.70 (s, 3H). LCMS (ES+) 385.1 (M+H)+, RT 2.45 minutes (Method 3).

Workup

  1. customwas degassed for 5 minutes
  2. customthe reaction mixture was degassed for a further 5 minutes
  3. customThe solvent was removed in vacuo
  4. customthe product obtained
  5. customThe mixture was partitioned between DCM (50 mL) and 10% aqueous K2CO3 solution (30 mL)
  6. dry with materialThe organic layer was dried (MgSO4)
  7. customthe solvent removed in vacuo
  8. customThe product obtained
  9. stirringAfter stirring at r.t. for 18 h
  10. washwashed with water (7×50 mL)
  11. customThe organic layer was separated
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. customthe solvent removed in vacuo
  15. customPurification by column chromatography (SiO2, 1-10% MeOH in DCM)

Sources & evidence

ORD record
ord-d3ccc9de898045fda0ba97c709ffff83
Source dataset
uspto-grants-2013_03
Patent number
US08399483B2

Reaction notes

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