Hydrochloric Acid → HCID 22890593, compound

HRID 993255Notes

Reaction equation

HRID 993255 reaction equation
CC(C[AlH]C[CH:7]([CH3:9])[CH3:8])C.N1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17]N=2)[CH:13]=[CH:12]C=1.S(C1C=CC(C)=CC=1)(O)(=O)=O.N[C@H](C1[CH:42]=[N:43][C:44]([O:47]C)=[CH:45]C=1)CC(OC(C)(C)C)=O.C[C:50]([O-:52])=[O:51].[Na+].[BH3-]C#[N:56].[Na+].Cl.[C:59]([O-:62])([O-])=O.[Na+].[Na+]>C1COCC1.CCOC(C)=O>[CH2:19]([O:52][C:50](=[O:51])[N:56]([CH2:9][CH:7]=[CH2:8])[CH2:45][C:44](=[O:47])[N:43]([O:62][CH3:59])[CH3:42])[C:14]1[CH:13]=[CH:12][CH:17]=[CH:16][CH:15]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 14487Diisobutylaluminum hydrideHCID 1360691,8-NaphthyridineHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 22890559HCID 22890559, compound

Product 1

HCID 22890593HCID 22890593, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIBAL-H (1.0M solution in hexanes, 8.80 ml, 8.80 mmol) was added dropwise to a stirred solution of 8-4 (2.00 g, 3.52 mmol) in 40 ml of anhydrous THF at −78° C. After 2 hours, the mixture was warmed to room temperature and quenched by slow addition of MeOH (1.6 ml ). A 1.0M aqueous Rochelle salt solution was added, and the mixture was stirred for 30 minutes. EtOAc was added, the organic layer was separated and dried with MgSO4, the solvent was removed under reduced pressure, and the crude product 8-5 was azeotroped with toluene, then dissolved in 40 ml of isopropanol. To the solution was added 3(S)-(6-methoxypyridin-3-yl)-β-alanine tert-butyl ester p-toluenesulfonic acid salt 1-5 (1.73 g, 4.22 mmol), NaOAc (2.89 g, 35.2 mmol), and 3.5 g of powdered molecular sieves. The mixture was stirred at room temperature for 12 hours and was cooled to 0° C., and NaCNBH3 (0.67 g, 10.6 mmol) was added in one portion. The mixture was then warmed to room temperature and stirred for 24 hours. 1H HCl was added to bring the pH to 2. After the mixture was stirred for 10 minutes, EtOAc was added, the pH was then adjusted to 11 with saturated aqueous Na2CO3. The organic portion was separated and dried with MgSO4, filtered, concentrated, and purified by flash silica gel column chromatography (0% to 10% of MeOH in EtOAc).

Workup

  1. customquenched by slow addition of MeOH (1.6 ml )
  2. additionA 1.0M aqueous Rochelle salt solution was added
  3. additionEtOAc was added
  4. customthe organic layer was separated
  5. dry with materialdried with MgSO4
  6. customthe solvent was removed under reduced pressure
  7. customthe crude product 8-5 was azeotroped with toluene
  8. dissolutiondissolved in 40 ml of isopropanol
  9. stirringThe mixture was stirred at room temperature for 12 hours
  10. temperaturewas cooled to 0° C.
  11. temperatureThe mixture was then warmed to room temperature
  12. stirringstirred for 24 hours
  13. stirringAfter the mixture was stirred for 10 minutes
  14. customThe organic portion was separated
  15. dry with materialdried with MgSO4
  16. filtrationfiltered
  17. concentrationconcentrated
  18. custompurified by flash silica gel column chromatography (0% to 10% of MeOH in EtOAc)

Sources & evidence

ORD record
ord-27ae08f6c09d42c9aa381def299ffa34
Source dataset
uspto-grants-2002_10
Patent number
US06472403B2

Reaction notes

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