Acetic Acid → Tert-Butyl 4-(3-(Isopropylamino)Pyridin-2-Yl)Piperazine-1-Carboxylate

HRID 1449706Notes

Reaction equation

HRID 1449706 reaction equation
[CH3:1][C:2]([CH3:20])([O:4][C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[C:18]([NH2:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:9][CH2:8]1)=[O:6])[CH3:3].[CH3:21][C:22]([CH3:24])=O.C(O)(=O)C.C([BH3-])#N.[Na+]>CO.C(Cl)(Cl)Cl>[CH3:3][C:2]([CH3:20])([O:4][C:5]([N:7]1[CH2:8][CH2:9][N:10]([C:13]2[C:18]([NH:19][CH:22]([CH3:24])[CH3:21])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:11][CH2:12]1)=[O:6])[CH3:1]

Participants

7

Reactant 4

HCID 176Acetic Acid2×HCID 180Acetone2×HCID 2756375tert-Butyl 4-(3-aminopyridin-2-yl)piperazine-1-carboxylateHCID 5003444Sodium cyanoborohydride2×

Product 1

HCID 10448702Tert-Butyl 4-(3-(Isopropylamino)Pyridin-2-Yl)Piperazine-1-Carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

1-[1,1-Dimethylethoxycarbonyl]4-[3-amino-2-pyridinyl]piperazine (International Publication 88/08424, 2.0 g) is dissolved in 35 ml of methanol and acetone (0.48 g) is added. The reaction is cooled to 0° and acetic acid (to pH 4.0) is added. The reaction is stirred 15 min at 0° and then sodium cyanoborohydride (0.50 g) is added. The reaction is allowed to warm slowly to 20-25° and followed by TLC until completion. Additional acetic acid, sodium cyanoborohydride and acetone arc sometimes necessary to force the reaction to completion. The reaction is diluted with chloroform (100 ml), washed with saturated aqueous sodium bicarbonate (50 ml), saline (75 ml), dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (75 g silica gel, 4:1 hexane/ethyl acetate) affords the title compound, NMR (300 MHz, CDCl3) 7.67, 6.91, 4.15, 3.57, 3.00, 1.48 and 1.23 δ.

Workup

  1. temperatureThe reaction is cooled to 0°
  2. temperatureto warm slowly to 20-25°
  3. customthe reaction to completion
  4. washwashed with saturated aqueous sodium bicarbonate (50 ml), saline (75 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography (75 g silica gel, 4:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-2c9ce1e5005e404aa9f2d0fcce020ea4
Source dataset
uspto-grants-1997_02
Patent number
US05599930

Reaction notes

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