Acetic Acid → 2-(Boc-piperazinyl)-3-(isopropylamino)pyridine

HRID 587414Notes

Reaction equation

HRID 587414 reaction equation
[NH2:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH:9]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:21][C:22]([CH3:24])=O.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>ClC(Cl)C>[C:14]([CH:9]1[CH2:10][NH:11][CH2:12][CH2:13][N:8]1[C:3]1[C:2]([NH:1][CH:22]([CH3:24])[CH3:21])=[CH:7][CH:6]=[CH:5][N:4]=1)([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 180AcetoneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 200680853-Amino-2-(Boc-piperazinyl)pyridine

Product 1

HCID 673768282-(Boc-piperazinyl)-3-(isopropylamino)pyridine

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

3-amino-2-(Boc-piperazine)pyridine 7 (3.813 g, about 11.16 mmol, crude) was dissolved in dichloroethane (75 mL). Acetone (1.7 mL, 23.12 mmol) was added, followed by an addition of HOAc (1.0 mL, 17.45 mmol) at room temperature. After about 10 min, NaBH(OAc)3 (7.46 g, 33.44 mmol) was added. An additional amount of dichloroethane (25 mL) was added. The resulting mixture was stirred at room temperature for 64 h. 5% aqueous NaHCO3 was added to quench the reaction. The organic phase was separated and the aqueous phase was extracted with dichloromethane (2×50 mL). The combined organic solution was washed with brine, dried over anhydrous Na2SO4, concentrated. The residue was purified via flash column chromatography over silica gel with 5-35% ethyl acetate in hexane to afford the product as solid in quantitative yield. 1H-NMR (CDCl3): 7.673 (dd, J=5.0 Hz and 1.5 Hz, 1 H, Ar—H), 6.904 (dd, J=8.0 Hz and 5.0 Hz, 1 H, Ar—H), 6.812 (dd, J=8.0 Hz and 1.5 Hz, 1 H, Ar—H), 4.150 (d, J=7.5 Hz, 1 H, NH), 3.569-3.517 (m, 5 H, 2CH2 and CH), 2.997 (t, J=5.0 Hz, 4 H, 2 CH2), 1.477 (s, 9 H, 3 CH3), 1.23 (d, J=6.0 Hz, 6 H, 2 CH3). (ref. Romero D. L. et al. J. Med. Chem. 37, 999-1014, 1994.)

Workup

  1. customto quench
  2. customthe reaction
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was extracted with dichloromethane (2×50 mL)
  5. washThe combined organic solution was washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified via flash column chromatography over silica gel with 5-35% ethyl acetate in hexane

Sources & evidence

ORD record
ord-a5d0d99811694dea9d55c8954b5a4190
Source dataset
uspto-grants-2016_01
Patent number
US09226970B2

Reaction notes

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