Triethylamine → 6,7-Dihydro-5H-cyclopenta[b]pyridin-6-amine

HRID 19735Notes

Reaction equation

HRID 19735 reaction equation
C([N:3]([CH2:6][CH3:7])[CH2:4][CH3:5])C.Cl.[N:9]1C2CC(C(O)=O)C[C:13]=2[CH:12]=[CH:11][CH:10]=1.ClC(OCC)=O.[N-]=[N+]=[N-].[Na+]>CC(C)=O.O.[Cl-].[Na+].O>[N:3]1[C:4]2[CH2:5][CH:10]([NH2:9])[CH2:11][C:12]=2[CH:13]=[CH:7][CH:6]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 33557Sodium AzideHCID 685628996,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylic acid hydrochloride

Product 1

HCID 450794946,7-Dihydro-5H-cyclopenta[b]pyridin-6-amine

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (1.50 ml, 10.79 mmol) is added to a cooled (0° C.) solution of 6,7-dihydro-5H-[1]pyrindine-6-carboxylic acid hydrochloride (1.00 g, 5.02 mmol) in acetone (8 ml) and water (1.6 ml), followed by dropwise addition of ethyl chloroformate (0.721 ml, 7.54 mmol) over S minutes. The reaction is stirred at 0° C. for 50 minutes, then a solution of sodium azide (0.521 g, 8.04 mmol) in water (3 ml) is added. After 1.5 hours, the reaction is poured into brine and extracted with ether. The combined ether extracts are dried (Na2SO4) and evaporated. The residue is taken into toluene (40 ml) and gradually heated to 100° C. until gas evolution ceases. The solvent is evaporated, the residue taken into 6N hydrochloric acid and heated to reflux for 16 hours. After evaporation, the crude hydrochloride salt is taken into MeOH and polymer supported trisamine (10 g) is added, followed by decolourising charcoal. The suspension is filtered through a Celite™ filter pad and the filtrate evaporated. The resultant material is purified by flash column chromatography (20:1 CH2Cl2-MeOH containing 1% triethylamine elution) to afford 6,7-dihydro-5H-[1]pyrindin-6-ylamine. δH 2.65 (1H dd J 15.9 5.1), 2.74 (1H dd J 16.6 5.1), 3.15 (1H dd J 16.1 7.0), 3.23 (1H dd J 16.6 7.0), 3.83 (1H m), 6.97 (1H dd J 6.9 4.8), 7.42 (1H d J 6.9), 8.28 (1H d J 4.8).

Workup

  1. waitAfter 1.5 hours
  2. extractionextracted with ether
  3. dry with materialThe combined ether extracts are dried (Na2SO4)
  4. customevaporated
  5. temperaturegradually heated to 100° C. until gas evolution ceases
  6. customThe solvent is evaporated
  7. temperatureheated
  8. temperatureto reflux for 16 hours
  9. customAfter evaporation
  10. additionis added
  11. filtrationThe suspension is filtered through a Celite™
  12. filtrationfilter pad
  13. customthe filtrate evaporated
  14. customThe resultant material is purified by flash column chromatography (20:1 CH2Cl2-MeOH containing 1% triethylamine elution)

Sources & evidence

ORD record
ord-55ee2a2d9a294ca1a8e1b363d6a284b6
Source dataset
uspto-grants-2010_06
Patent number
US07745462B2

Reaction notes

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