Hydrochloric Acid → HCID 178426582, compound

HRID 2109040Notes

Reaction equation

HRID 2109040 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[O:9]=[C:10]1[CH2:15][O:14][CH2:13][CH2:12][N:11]1[C@H:16]1[CH2:21][CH2:20][C@H:19]([C:22]([NH:24][C:25]2[C:29]3=[N:30][CH:31]=[CH:32][CH:33]=[C:28]3[O:27][C:26]=2[C:34](OC)=[O:35])=[O:23])[CH2:18][CH2:17]1.Cl.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:34]([C:26]2[O:27][C:28]3[C:29](=[N:30][CH:31]=[CH:32][CH:33]=3)[C:25]=2[NH:24][C:22]([C@H:19]2[CH2:20][CH2:21][C@H:16]([N:11]3[CH2:12][CH2:13][O:14][CH2:15][C:10]3=[O:9])[CH2:17][CH2:18]2)=[O:23])=[O:35])=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 153482-Amino-5-methylpyridineHCID 516892Sodium BicarbonateHCID 178499199HCID 178499199, compound

Product 1

HCID 178426582HCID 178426582, compoundYield 61.6%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

2-Amino-5-methylpyridine (81 mg) is dissolved in chloroform (5 ml). After adding 0.98 M trimethyl alminum-hexane solution (763 μl) under ice-cooling, the reaction solution is stirred under ice-cooling for 10 minutes, and then at room temperature for 0.5 hours. To the resulting reaction solution is added methyl 3-({[trans-4-(3-oxomorpholin-4-yl)cyclohexyl]carbonyl}amino)furo[3,2-b]pyridine-2-carboxylate (150 mg) obtained in Reference Example 79, and the mixture is stirred at room temperature for 2 hours and at 50° C. under heating for 5 hours. To the reaction solution is added 10% hydrochloric acid (3 ml) under ice-cooling, and the mixture is stirred at room temperature for 0.5 hours. The reaction solution is then neutralized by adding saturated aqueous sodium hydrogen carbonate solution, and extracted with chloroform. The organic layer is washed with saturated brine, dried over sodium sulfate, and the solvent is evaporated under reduced pressure. The residue is purified by NH-silica gel column chromatography (eluent: ethyl acetate followed by ethyl acetate/methanol=10/1). The resulting solid is suspended in diethyl ether, and collected by filtration to give the title compound (110 mg).

Workup

  1. additionAfter adding 0.98 M trimethyl alminum-hexane solution (763 μl) under ice-
  2. temperaturecooling
  3. temperaturecooling for 10 minutes
  4. customTo the resulting reaction solution
  5. customobtained in Reference Example 79
  6. stirringthe mixture is stirred at room temperature for 2 hours and at 50° C.
  7. temperatureunder heating for 5 hours
  8. temperaturecooling
  9. stirringthe mixture is stirred at room temperature for 0.5 hours
  10. extractionextracted with chloroform
  11. washThe organic layer is washed with saturated brine
  12. dry with materialdried over sodium sulfate
  13. customthe solvent is evaporated under reduced pressure
  14. customThe residue is purified by NH-silica gel column chromatography (eluent: ethyl acetate followed by ethyl acetate/methanol=10/1)
  15. filtrationcollected by filtration

Sources & evidence

ORD record
ord-5d4253a68d7e4a83a6d4a5f344be7462
Source dataset
uspto-grants-2009_04
Patent number
US07514449B2

Reaction notes

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