Pyridine → HCID 86673681, compound

HRID 2273058Notes

Reaction equation

HRID 2273058 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]([NH:11][CH2:12][CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:22]1[C@H:26]([OH:27])[C@H:25]([OH:28])[C@@H:24]([CH2:29]O)[O:23]1.S(Cl)([Cl:33])=O.N1C=CC=CC=1>C(#N)C>[NH2:1][C:2]1[N:10]=[C:9]([NH:11][CH2:12][CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:22]1[C@H:26]([OH:27])[C@H:25]([OH:28])[C@@H:24]([CH2:29][Cl:33])[O:23]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 71042226HCID 71042226, compound

Product 1

HCID 86673681HCID 86673681, compoundYield 16.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stifling mixture consisting of Compound 18 (1.03 g, 2.42 mmol) and acetonitrile (80 mL) under a nitrogen atmosphere and cooled over an ice-acetone bath was added thionyl chloride (0.53 mL, 7.3 mmol). The reaction mixture continued stirring cold for 15 minutes and was subsequently treated with pyridine (0.469 g, 4.84 mmol) with dropwise addition. An immediate color change was observed, and the mixture was stirred cold for another 45 minutes. The cold bath was removed and the mixture was allowed to stir overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in methanol. The ice bath-cooled mixture under a nitrogen atmosphere was treated with ammonium hydroxide solution to pH 10. The resulting mixture was stirred for 1.5 hours, as it was allowed to warm to room temperature. The mixture was concentrated under reduced pressure, and the residue was purified by silica column (80 g) chromatography. Elution with a gradient (100% dichloromethane to 10% methanol in dichloromethane), combination of fractions containing separated desired product, and concentration under reduced pressure afforded the title intermediate (0.175 g, 16.4% yield) as a white solid; 1H NMR (400 MHz, DMSO-d6) δ 7.87 (s, 1 H), 6.81 (t, 1H, J=5.5 Hz), 6.73 (s, 2H), 6.26 (t, 1H, J=5.5 Hz), 5.73 (d, 1H, J=5.5 Hz), 5.47 (d, 1H, J=5.9 Hz), 5.36 (d, 1H, J=5.1 Hz), 4.75 (broad m, 1 H), 4.20 (m, 1H), 4.01 (m, 1H), 3.90 (dd, 1H, 11.4, 5.2 Hz), 3.79 (m, 1H), 3.23 (m, 2H), 3.08 (m, 2H), 2.06 (s, 2H), 1.34 (s, 9H); LC/MS (ESI+) m/z 444.

Workup

  1. temperaturecooled over an ice-acetone bath
  2. stirringthe mixture was stirred cold for another 45 minutes
  3. customThe cold bath was removed
  4. stirringto stir overnight at room temperature
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. dissolutionthe residue was dissolved in methanol
  7. temperatureThe ice bath-cooled mixture under a nitrogen atmosphere
  8. additionwas treated with ammonium hydroxide solution to pH 10
  9. stirringThe resulting mixture was stirred for 1.5 hours, as it
  10. concentrationThe mixture was concentrated under reduced pressure
  11. customthe residue was purified by silica column (80 g) chromatography
  12. washElution with a gradient (100% dichloromethane to 10% methanol in dichloromethane), combination of fractions
  13. additioncontaining
  14. customseparated
  15. concentrationdesired product, and concentration under reduced pressure

Sources & evidence

ORD record
ord-da9950558feb4a70be75d0aacfcb32cd
Source dataset
uspto-grants-2015_09
Patent number
US09120820B2

Reaction notes

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