Toluene → N3-ethyl-6-propyl-pyridine-3,4-diamine

HRID 895560Notes

Reaction equation

HRID 895560 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][CH3:10])[N:5]=[CH:4][C:3]=1[NH:11][C:12](=O)[CH3:13].C(N(C)C)C.[AlH3].C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.C(Cl)Cl>[CH2:12]([NH:11][C:3]1[CH:4]=[N:5][C:6]([CH2:8][CH2:9][CH3:10])=[CH:7][C:2]=1[NH2:1])[CH3:13]

Participants

8

Reactant 5

HCID 1140Toluene2×HCID 10340Sodium CarbonateHCID 11723Dimethylethylamine2×HCID 14488Aluminum hydride2×HCID 22380205N-(4-amino-6-propyl-pyridin-3-yl)-acetamide

Product 1

HCID 86587614N3-ethyl-6-propyl-pyridine-3,4-diamine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of the crude N-(4-amino-6-propyl-pyridin-3-yl)-acetamide (114 mg, 0.59 mmol) in THF (2.5 mL) at 0° C. under N2 is treated with 0.5 M EtNMe2.AlH3 in toluene (2.4 mL, 1.18 mmol). The reaction mixture is stirred for 4 h while slowly warming to rt, whereupon it is treated with additional 0.5 M EtNMe2.AlH3 in toluene (2.4 mL, 1.18 mmol). After stirring at room temperature overnight, the reaction mixture is cooled to 0° C. and treated with moist Na2CO3. The mixture is diluted with CH2Cl2 and stirred vigorously for 15 min. It is then filtered through a pad of Celite, and the filtrate concentrated. The crude material is partially purified by preparative thin layer chromatography, developing with 15:1 CHCl3-MeOH (+1% Et3N). The band containing the desired N3-ethyl-6-propyl-pyridine-3,4-diamine does not separate well from the approximately 10% of the slightly more polar, unreacted N-(4-amino-6-propyl-pyridin-3-yl)-acetamide. Both bands are collected, and the mixture is carried into the next reaction. 1H NMR (CDCl3, 300 MHz) δ 7.74 (s, 1H), 6.42 (s, 1H), 4.10 (br, 1H), 3.67 (m, 1H), 3.10 (q, J=7.2 Hz, 2H), 2.56 (m, 2H), 1.67 (sextet, J=7.2 Hz, 2H), 1.25 (t, J=7.2 Hz, 3H), 0.91 (t, J=7.2 Hz, 3H) ppm. Electrospray MS: m/z 180 [M+1].

Workup

  1. stirringAfter stirring at room temperature overnight
  2. temperaturethe reaction mixture is cooled to 0° C.
  3. stirringstirred vigorously for 15 min
  4. filtrationIt is then filtered through a pad of Celite
  5. concentrationthe filtrate concentrated
  6. customThe crude material is partially purified by preparative thin layer chromatography
  7. additionThe band containing the desired N3-ethyl-6-propyl-pyridine-3,4-diamine
  8. customdoes not separate well from the approximately 10% of the slightly more polar, unreacted N-(4-amino-6-propyl-pyridin-3-yl)-acetamide
  9. customBoth bands are collected
  10. customthe mixture is carried into the next reaction

Sources & evidence

ORD record
ord-d77366d2a92749a3abbda7db41fb596a
Source dataset
uspto-grants-2005_07
Patent number
US06916819B2

Reaction notes

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