2,3-Diaminopyridine → tert-Butyl 4-[(2-aminopyridin-3-yl)amino]piperidine-1-carboxylate

HRID 14379

Reaction equation

HRID 14379 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH2:15][C:16]1[C:21]([NH2:22])=[CH:20][CH:19]=[CH:18][N:17]=1.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][C:33](=O)[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24]>ClC(Cl)C>[NH2:15][C:16]1[C:21]([NH:22][CH:33]2[CH2:34][CH2:35][N:30]([C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:29])[CH2:31][CH2:32]2)=[CH:20][CH:19]=[CH:18][N:17]=1

Participants

5

Reactant 3

HCID 99562,3-DiaminopyridineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride2×

Product 1

HCID 22293217tert-Butyl 4-[(2-aminopyridin-3-yl)amino]piperidine-1-carboxylateYield 33.2%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (14.5 g, 68.7 mmol) was added to a solution of 2,3-diaminopyridine (5.00 g, 45.8 mmol) and N-(tert-butoxycarbonyl)-4-piperidone (9.58 g, 48.1 mmol) in dichloroethane (75 mL) at room temperature. After 5 h, additional sodium triacetoxyborohydride was added (1.8 g) and again after another 2.5 h. The reaction was stirred overnight, and quenched with 5% aqueous sodium hydroxide. This was extracted with methylene chloride, and washed with 5% aqueous sodium hydroxide, water and saturated sodium chloride solution. After drying over sodium sulfate, the solution was filtered and evaporated to give the crude product. This was purified by chromatography (silica gel, 3 to 5% methanol in methylene chloride gradient elution), which gave the title compound (4.44 g). MS 293 (M+1) 1H NMR (500 MHz, CD3OD) δ 7.32 (dd, J=5, 1 Hz, 1H), 6.85 (dd, J=8, 1 Hz, 1H), 6.59 (dd, J=8, 5 Hz, 1H), 4.04 (d, J=13 Hz, 2H), 3.46 (m, 1H), 2.98 (br s, 2H), 2.01 (dd, J=12, 2 Hz, 2H), 1.46 (s, 9H), 1.37 (qd, J=12, 4 Hz, 2H).

Workup

  1. waitagain after another 2.5 h
  2. customquenched with 5% aqueous sodium hydroxide
  3. extractionThis was extracted with methylene chloride
  4. washwashed with 5% aqueous sodium hydroxide, water and saturated sodium chloride solution
  5. dry with materialAfter drying over sodium sulfate
  6. filtrationthe solution was filtered
  7. customevaporated
  8. customto give the crude product
  9. customThis was purified by chromatography (silica gel, 3 to 5% methanol in methylene chloride gradient elution), which

Sources & evidence

ORD record
ord-9a838bdd34ad464698717d23dc8fc819
Source dataset
uspto-grants-2010_06
Patent number
US07732438B2

Linked notes

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