Acetic Acid → 1-Benzyl-4-[N-ethyl-N-(6-fluoro-3-(isopropylamino)-2-pyridinyl)amino]piperidine

HRID 361854Notes

Reaction equation

HRID 361854 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH2:25][CH3:26])[C:15]2[C:20]([N+:21]([O-])=O)=[CH:19][CH:18]=[C:17]([F:24])[N:16]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:27](N1CCC(N(CC)C2C(N)=CC=C(F)N=2)CC1)[C:28]1C=CC=C[CH:29]=1.CC(C)=O.C(O)(=O)C.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>C(O)C.CO.[Pt]=O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH2:25][CH3:26])[C:15]2[C:20]([NH:21][CH:28]([CH3:29])[CH3:27])=[CH:19][CH:18]=[C:17]([F:24])[N:16]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 180AcetoneHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 105945621-Benzyl-4-[N-ethyl-N-(6-fluoro-3-nitro-2-pyridyl)amino]piperidineHCID 106162651-benzyl-4-[N-ethyl-N-(6-fluoro-3-(amino)-2-pyridinyl)amino]piperidine

Product 1

HCID 105712191-Benzyl-4-[N-ethyl-N-(6-fluoro-3-(isopropylamino)-2-pyridinyl)amino]piperidine

Reagents, catalysts & solvents 3

HCID 82844Platinum oxide (PtO)CatalystHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

1-Benzyl-4-[N-ethyl-N-(6-fluoro-3-(nitro)-2-pyridinyl)amino]piperidine (EXAMPLE 195, 3.0 g, 8.37 mmol) is dissolved in ethanol (500 ml) and 0.75 g of platinum oxide is added. The reaction is placed on a Parr hydrogenator at 10 psi for 1 hr and then filtered through diatomaceous earth and concentrated under reduced pressure. The crude 1-benzyl-4-[N-ethyl-N-(6-fluoro-3-(amino)-2-pyridinyl)amino]piperidine (3.0 g, 9.13 mmol) is immediately dissolved in methanol (18 ml) and acetone (0.74 ml, 10.04 mmol) and acetic acid (13.1 ml, 228.3 mmol) are added. The reaction is stirred for 10 min, then cooled to 0° and sodium cyanoborohydride (0.61 g, 9.7 mmol) is added. The reaction is slowly warmed to 20°-25° and stirred for 18 hr. Then solid sodium bicarbonate is added with caution and the reaction is extracted with chloroform, washed with saline, dried over sodium sulfate and concentrated under reduced pressure. Purification via flash column chromatography (5% ethyl acetate/hexane to 10% ethyl acetate/hexane) gives the title compound, NMR (300 MHz, CDCl3) 7.26-7.15, 6.88, 6.49, 4.28, 3.40, 3.44, 3.04, 2.93, 2.82, 1.93, 1.72-1.52, 1.13 and 0.81δ; CMR (CDCl3, 75 MHz) 155.9, 152.5, 146.1, 138.0, 129.1, 128.1, 126.9, 121.8, 104.3, 62.9, 57.5, 52.7, 44.4, 41.2, 29.7 and 22.8δ.

Workup

  1. filtrationfiltered through diatomaceous earth
  2. concentrationconcentrated under reduced pressure
  3. temperaturecooled to 0°
  4. temperatureThe reaction is slowly warmed to 20°-25°
  5. stirringstirred for 18 hr
  6. extractionthe reaction is extracted with chloroform
  7. washwashed with saline
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customPurification via flash column chromatography (5% ethyl acetate/hexane to 10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e9cd92ef2bf94896943f58dd815e063b
Source dataset
uspto-grants-1999_02
Patent number
US05866589

Reaction notes

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