Acetic Acid → HCID 66938955, compound

HRID 1716928Notes

Reaction equation

HRID 1716928 reaction equation
C(C1C=CC(C([Cl:9])=O)=CC=1)#N.NC1C=CC=C(N)N=1.[OH-].[Na+].[NH2:22][C:23]1[N:28]=[C:27]([NH:29][C:30](=[O:39])[C:31]2[CH:36]=[CH:35][C:34]([C:37]#[N:38])=[CH:33][CH:32]=2)[CH:26]=[CH:25][CH:24]=1.[CH3:40][N:41]1[CH2:46][CH2:45][C:44](=O)[CH2:43][CH2:42]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH4+].[Cl-]>C1COCC1.O.O1CCOCC1>[ClH:9].[C:37]([C:34]1[CH:35]=[CH:36][C:31]([C:30]([NH:29][C:27]2[CH:26]=[CH:25][CH:24]=[C:23]([NH:22][CH:44]3[CH2:45][CH2:46][N:41]([CH3:40])[CH2:42][CH2:43]3)[N:28]=2)=[O:39])=[CH:32][CH:33]=1)#[N:38]

Participants

12

Reactant 8

HCID 176Acetic AcidHCID 88612,6-DiaminopyridineHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 740491-Methyl-4-piperidoneHCID 801724-Cyanobenzoyl chlorideHCID 5049666Sodium triacetoxyborohydrideHCID 66939201HCID 66939201, compound

Product 1

HCID 66938955HCID 66938955, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

Combine 4-cyanobenzoyl chloride (300 μL, 1.80 mmol), 2,6-diaminopyridine (600 mg, 5.5 mmol, and dioxane (10 mL); stir at room temperature for 2 hr. Pour into water and adjust to pH>12 by the addition of 5N NaOH. Extract with CH2Cl2 twice, combine organics, dry over MgSO4, and concentrate. Chromatograph (silica gel, eluting with 0-10% methanol/CH2Cl2). Dissolve the purified intermediate N-(6-amino-pyridin-2-yl)-4-cyano-benzamide (202 mg, 0.84 mmol, 47%) in THF (10 mL). Add to this 1-methyl-4-piperidone (77 mg, 0.68 mmol), acetic acid (150 μL, 2.5 mmol), and sodium triacetoxyborohydride (440 mg, 2.10 mmol). Stir the reaction at room temperature for 18 hr, and quench by the addition of saturated aqueous NaHCO3. Extract the aqueous layer with ethylacetate twice, wash the combined organics with saturated aqueous NaCl, dry over MgSO4, and concentrate. Chromatograph the material (silica gel, eluting with 0-20% 2M NH3 in methanol/CH2Cl2). Dissolve the clean material (10.4 mg, 5%) in methanol and add 1 equivalent (1.7 mg) of NH4Cl. Sonicate the reaction at room temperature for 15 min, then concentrate to provide the title compound: mass spectrum (ion spray): m/z=336.0 (M+1).

Workup

  1. extractionExtract with CH2Cl2 twice
  2. dry with materialdry over MgSO4
  3. concentrationconcentrate
  4. washChromatograph (silica gel, eluting with 0-10% methanol/CH2Cl2)
  5. stirringStir
  6. customthe reaction at room temperature for 18 hr
  7. customquench by the addition of saturated aqueous NaHCO3
  8. extractionExtract the aqueous layer with ethylacetate twice
  9. washwash the combined organics with saturated aqueous NaCl
  10. dry with materialdry over MgSO4
  11. concentrationconcentrate
  12. washChromatograph the material (silica gel, eluting with 0-20% 2M NH3 in methanol/CH2Cl2)
  13. dissolutionDissolve the clean material (10.4 mg, 5%) in methanol
  14. customSonicate
  15. customthe reaction at room temperature for 15 min
  16. concentrationconcentrate

Sources & evidence

ORD record
ord-911ef244dfa2418aa9be0a2a7c3472b9
Source dataset
uspto-grants-2010_09
Patent number
US07803813B2

Reaction notes

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