Sodium Bicarbonate → 5-(4-{4-[5-(4-chloropyridine-2-yl)-1H-[1,2,4]triazole-3-yl]-piperidine-1-ylmethyl}-phenyl)-2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine

HRID 1851298Notes

Reaction equation

HRID 1851298 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[NH:9][N:10]=[C:11]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[N:12]=2)[CH:3]=1.C1([C:22]2[CH:29]=[C:28]([C:30]3[C:35]([C:36]4[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=4)=[CH:34][N:33]4[N:43]=[CH:44][N:45]=[C:32]4[N:31]=3)[CH:27]=[CH:26][C:23]=2[CH:24]=O)CC1.[BH-](O[C:56]([CH3:58])=O)(OC(C)=O)OC(C)=O.[Na+].[C:60]([O-])(O)=O.[Na+]>CN1C(=O)CCC1.C(O)(=O)C.C(N(CC)CC)C>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[NH:9][N:10]=[C:11]([CH:13]3[CH2:18][CH2:17][N:16]([CH2:24][C:23]4[CH:26]=[CH:27][C:28]([C:30]5[C:35]([C:36]6[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=6)=[CH:34][N:33]6[N:43]=[C:44]([CH:58]7[CH2:56][CH2:60]7)[N:45]=[C:32]6[N:31]=5)=[CH:29][CH:22]=4)[CH2:15][CH2:14]3)[N:12]=2)[CH:3]=1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 867030522-Cyclopropyl-4-[6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]-benzaldehydeHCID 178478250HCID 178478250, compound

Product 1

HCID 1785055245-(4-{4-[5-(4-chloropyridine-2-yl)-1H-[1,2,4]triazole-3-yl]-piperidine-1-ylmethyl}-phenyl)-2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidineYield 25.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8471TriethylamineSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

412 mg 4-Chloro-2-(5-piperidine-4-yl-2H-[1,2,4]triazole-3-yl)-pyridine×2HCl are dissolved in 7.2 mL NMP. After addition of 0.28 mL triethylamine the reaction mixture is stirred for one hour. 600 mg 2-Cyclopropyl-4-[6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]-benzaldehyde (50% pure) and 0.09 mL acetic acid are added. The reaction mixture is stirred over night at room temperature. 191 mg (0.92 mmol) NaBH(OAc)3, are added in portions and the reaction mixture is stirred at room temperature for three days. After treatment of the reaction mixture with saturated NaHCO3 and stirring for one hour no solid precipitates. 200 mL tert.butyl-methylether are added and the mixture is stirred for one hour. After separation the organic phase is washed twice with water, dried and the solvent evaporated. Due to some remaining product in the aqueous phase this phase is extracted twice with tert.butyl-methylether (200 mL each). The combined organic phases are washed and dried. After removal of the solvent the residue is purified by chromatography on silica gel (dichloromethane/methanol). 134 mg (25.1%) of the pure product and additional 92.5 mg (18.2%) of the slightly contaminated product are obtained.

Workup

  1. stirringThe reaction mixture is stirred over night at room temperature
  2. stirringthe reaction mixture is stirred at room temperature for three days
  3. customprecipitates
  4. addition200 mL tert.butyl-methylether are added
  5. stirringthe mixture is stirred for one hour
  6. customAfter separation the organic phase
  7. washis washed twice with water
  8. customdried
  9. customthe solvent evaporated
  10. extractionDue to some remaining product in the aqueous phase this phase is extracted twice with tert.butyl-methylether (200 mL each)
  11. washThe combined organic phases are washed
  12. customdried
  13. customAfter removal of the solvent the residue
  14. customis purified by chromatography on silica gel (dichloromethane/methanol)

Sources & evidence

ORD record
ord-3a9dddeeee374b4ca7f2a1c32398db08
Source dataset
uspto-grants-2015_02
Patent number
US08957064B2

Reaction notes

Loading…