Potassium Carbonate → HCID 67201028, compound

HRID 1948740Notes

Reaction equation

HRID 1948740 reaction equation
Cl[C:2]1[C:11]([CH2:12]O)=[CH:10][C:9]2[C:4](=[C:5]([CH3:15])[CH:6]=[CH:7][C:8]=2[Cl:14])[N:3]=1.[C:16]1([CH3:25])[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O.C([O-])([O-])=O.[K+].[K+].P(Br)(Br)Br.[SH:36][C:37]1[N:45]=[CH:44][N:43]=[C:42]2[C:38]=1[NH:39][CH:40]=[N:41]2>COCCOC.O.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>[Cl:14][C:8]1[CH:7]=[CH:6][C:5]([CH3:15])=[C:4]2[C:9]=1[CH:10]=[C:11]([CH2:12][S:36][C:37]1[N:45]=[CH:44][N:43]=[C:42]3[C:38]=1[NH:39][CH:40]=[N:41]3)[C:2]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH3:25])=[N:3]2

Participants

11

Reactant 5

HCID 11430Potassium Carbonate2×HCID 24614Phosphorus tribromideHCID 27332672-Methylphenyl boronic acidHCID 24276151(2,5-Dichloro-8-methylquinolin-3-yl)methanolHCID 178527888HCID 178527888, compound

Product 1

HCID 67201028HCID 67201028, compoundYield 32.5%

Reagents, catalysts & solvents 5

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

Conditions

Temperature
120 °C

Procedure

A mixture of (2,5-dichloro-8-methylquinolin-3-yl)methanol (500 mg, 2.06 mmol), o-tolylboronic acid (337 mg, 2.48 mmol) and K2CO3 (428 mg, 3.09 mmol) in DME (8 mL) and water (2 mL) was degassed by bubbling N2 through it for 5 minutes. Pd(PPh3)4 (119 mg, 0.1 mmol) was added and the reaction mixture was degassed for a further 5 minutes and then heated to 120° C. under microwave irradiation for 1 h. The solvent was removed in vacuo and the product was dissolved in DCM (40 mL). To this solution was added phosphorus tribromide (1.34 mL, 14.23 mmol) and the reaction mixture was stirred at r.t. for 3 h. The mixture was partitioned between DCM (100 mL) and 10% aqueous K2CO3 solution (50 mL). The organic layer was separated, dried (MgSO4) and the solvent removed in vacuo. The product obtained was dissolved in DMF (10 mL) and to this solution was added K2CO3 (147 mg, 1.06 mmol) and 6-mercaptopurine (180 mg, 1.06 mmol). The reaction mixture was stirred at r.t. for 18 h. The mixture was diluted with EtOAc (150 mL) and was washed with water (7×50 mL). The organic layer was separated, dried (MgSO4) and the solvent removed in vacuo. Purification by column chromatography (SiO2, 0-5% MeOH in DCM), then by preparative HPLC (Method 1), gave the title compound (149 mg, 16%) as an off-white solid. δH (DMSO-d6) 13.48 (br s, 1H), 8.86 (s, 1H), 8.62 (s, 1H), 8.43 (s, 1H), 7.66 (d, J 9 Hz, 1H), 7.59 (d, J 9 Hz, 1H), 7.35 (m, 4H), 4.68 (br s, 2H), 2.62 (s, 3H), 2.12 (s, 3H). LCMS (ES+) 432.2, 434.1 (M+H)+, RT 4.25 minutes (Method 3).

Workup

  1. customwas degassed
  2. customby bubbling N2 through it for 5 minutes
  3. customthe reaction mixture was degassed for a further 5 minutes
  4. customThe solvent was removed in vacuo
  5. dissolutionthe product was dissolved in DCM (40 mL)
  6. customThe mixture was partitioned between DCM (100 mL) and 10% aqueous K2CO3 solution (50 mL)
  7. customThe organic layer was separated
  8. dry with materialdried (MgSO4)
  9. customthe solvent removed in vacuo
  10. customThe product obtained
  11. stirringThe reaction mixture was stirred at r.t. for 18 h
  12. washwas washed with water (7×50 mL)
  13. customThe organic layer was separated
  14. dry with materialdried (MgSO4)
  15. customthe solvent removed in vacuo
  16. customPurification by column chromatography (SiO2, 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-b84aaf3ea3ed47d397d3f7426a132666
Source dataset
uspto-grants-2013_03
Patent number
US08399483B2

Reaction notes

Loading…