Tert-butyl (5-cyano-6-methoxy-4-methylpyridin-2-yl)carbamate → Tert-butyl (5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)carbamate

HRID 1477030Notes

Reaction equation

HRID 1477030 reaction equation
[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([C:15]#[N:16])=[C:10]([O:17][CH3:18])[N:9]=1)([CH3:4])([CH3:3])[CH3:2]>CC(O)=O.C(O)C.[Ni]>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([CH2:15][NH2:16])=[C:10]([O:17][CH3:18])[N:9]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 1

HCID 86677356Tert-butyl (5-cyano-6-methoxy-4-methylpyridin-2-yl)carbamate

Product 1

HCID 71276137Tert-butyl (5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)carbamateYield 68.9%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolvent

Procedure

A clear solution of tert-butyl(5-cyano-6-methoxy-4-methylpyridin-2-yl)carbamate (0.60 g, 2.279 mmol) in HOAc (5 mL) and ethanol (20 mL) was treated on an H-Cube apparatus (50 psi, 40° C., 1 mL/min., Raney Nickel cartridge) for 18 hr. LCMS showed that the reaction was complete (86% pure). The reaction was evaporated to dryness under vacuum. Purified by silica gel chromatography (Analogix, SF25-60 g, 0 to 12% (5% NH4OH/MeOH) in CH2Cl2). The pure fractions were combined and evaporated to dryness under vacuum to give the product tert-butyl(5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)carbamate (0.42 g, 1.571 mmol, 68.9% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 9.33 (s, 1H), 7.16 (s, 1H), 3.80 (s, 3H), 3.57 (s, 2H), 2.28 (s, 3H), 1.46 (s, 9H). MS(ES)+m/e 268.1 [M+H]+.

Workup

  1. customThe reaction was evaporated to dryness under vacuum
  2. customPurified by silica gel chromatography (Analogix
  3. customevaporated to dryness under vacuum

Sources & evidence

ORD record
ord-643b9e0c4f0c4073a723e2051c929d5e
Source dataset
uspto-grants-2016_08
Patent number
US09402836B2

Reaction notes

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