Ammonium formate → tert-Butyl (1-pyridazin-3-ylpiperidin-4-yl)carbamate

HRID 2421974

Reaction equation

HRID 2421974 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C([O-])=O.[NH4+]>CO.[Pd]>[N:7]1[CH:2]=[CH:3][CH:4]=[C:5]([N:8]2[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:18])[CH3:20])[CH2:10][CH2:9]2)[N:6]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formate2×HCID 379672514-(Boc-amino)-1-(6-chloro-3-pyridazinyl)piperidine

Product 1

HCID 86625871tert-Butyl (1-pyridazin-3-ylpiperidin-4-yl)carbamateYield 57%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl [1-(6-chloropyridazin-3-yl)piperidin-4-yl]carbamate (0.5 g, 1.60 mmol) was dissolved in MeOH (20 ml) and cooled to 0° C. with an icebath. 10% Pd/C (60 mg) was added carefully. Ammonium formate (0.30 g, 4.80 mmol) was added and the reaction mixture was heated to 40° C. Ammonium formate (0.604 g, 9.59 mmol) was added in portions during the reaction, after 33 h at 40° C. the reaction mixture was filtered through celite and the celite was washed with MeOH (20 ml). The reaction mixture was evaporated and the residue was diluted with EtOAc (100 mL) and washed with water (200 ml). The organic phase was dried (Na2SO4) filtered and evaporated. The residue was purified by silica gel column chromatography using a 98:2 mixture of DCM:MeOH to give the title compound as a solid (0.25 g, 57%). 1H NMR (CDCl3, 500 MHz): δ 8.52-8.47 (m, 1H), 7.17-7.11 (m, 1H), 6.91-6.84 (m, 1H), 4.67-4.57 (m, 1H), 4.30-4.21 (m, 2H), 3.75-3.62 (m, 1H), 3.09-2.99 (m, 2H), 2.05-1.96 (m, 2H), 1.46-1.35 (m, 2H), 1.40 (s, 9H); 13C NMR (CDCl3, 125 MHz): δ 160.0, 155.4, 143.3, 127.5, 112.7, 79.6, 48.2, 44.3, 32.1, 28.6.

Workup

  1. temperaturethe reaction mixture was heated to 40° C
  2. filtrationwas filtered through celite
  3. washthe celite was washed with MeOH (20 ml)
  4. customThe reaction mixture was evaporated
  5. additionthe residue was diluted with EtOAc (100 mL)
  6. washwashed with water (200 ml)
  7. dry with materialThe organic phase was dried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by silica gel column chromatography
  11. additiona 98:2 mixture of DCM

Sources & evidence

ORD record
ord-a297edd2b87941a89c66d78d0609517a
Source dataset
uspto-grants-2011_06
Patent number
US07960380B2

Linked notes

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