Acetic Acid → 1-tert-Butyloxycarbonyl-4-[N-methyl-N-(3-cyclopropylmethylamino-2-pyridinyl)amino]piperidine

HRID 361834Notes

Reaction equation

HRID 361834 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH3:22])[C:15]2[C:20]([NH2:21])=[CH:19][CH:18]=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:23]1[CH:25]([CH:26](O)C#N)[CH2:24]1.C([BH3-])#N.[Na+].C(O)(=O)C.[OH-].[Na+]>CO.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH3:22])[C:15]2[C:20]([NH:21][CH2:26][CH:25]3[CH2:23][CH2:24]3)=[CH:19][CH:18]=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydride2×HCID 106624511-(1,1-dimethylethoxycarbonyl)-4-[N-methyl-N-(3-amino-2-pyridinyl)amino]piperidineHCID 113893592-Cyclopropyl-2-hydroxyacetonitrile2×

Product 1

HCID 107610091-tert-Butyloxycarbonyl-4-[N-methyl-N-(3-cyclopropylmethylamino-2-pyridinyl)amino]piperidine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

1-tert-Butyloxycarbonyl-4-[N-methyl-N-(3-amino-2-pyridinyl)amino]piperidine (1.64 g, 5.37 mmol) is dissolved in methanol (0.2M) and cooled to 0°. Cyclopropylcarboxaldehyde (0.40 ml, 5.37 mmol) is added. After stirring 5 min, sodium cyanoborohydride (337 mg, 5.37 mmol) is added. The reaction is refluxed one hour, then stirred overnight at 20°-25°. Acetic acid (53.7 mmol) is added and the reaction refluxed 3 hr. After cooling to 20°-25°, cyclopropylcarboxaldehyde (820 mg, 2.68 mmol) and sodium cyanoborohydride (168 mg 2.68 mmol) are added and the reaction stirred 16 hr at 20°-25°. The mixture is diluted with water, adjusted to pH 9 with sodium hydroxide (1N) and extracted with chloroform. The extract is filtered and concentrated. The concentrate is chromatographed (silica gel; ethyl acetate/hexane (20/80) to give the title compound; NMR (300 MHz, CD3OD) 7.39, 6.79, 3.79, 3.07, 2.80, 2.63, 2.44, 1.52, 1.33, 1.27, 0.93, 0.35 and 0.05δ.

Workup

  1. temperaturecooled to 0°
  2. temperatureThe reaction is refluxed one hour
  3. stirringstirred overnight at 20°-25°
  4. temperaturethe reaction refluxed 3 hr
  5. temperatureAfter cooling to 20°-25°
  6. stirringthe reaction stirred 16 hr at 20°-25°
  7. extractionextracted with chloroform
  8. filtrationThe extract is filtered
  9. concentrationconcentrated
  10. customThe concentrate is chromatographed (silica gel

Sources & evidence

ORD record
ord-afbc5999df1a4e0aaf190ee179d4d88e
Source dataset
uspto-grants-1999_02
Patent number
US05866589

Reaction notes

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