Methylamine → Ethyl 6-chloro-4-(methylamino)pyridine-3-carboxylate

HRID 1430460Notes

Reaction equation

HRID 1430460 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4]([Cl:13])[CH:3]=1.[CH3:14][NH2:15]>CC#N>[Cl:13][C:4]1[CH:3]=[C:2]([NH:15][CH3:14])[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=1

Participants

4

Reactant 2

HCID 6329MethylamineHCID 600045Ethyl 4,6-dichloropyridine-3-carboxylate

Product 1

HCID 20627001Ethyl 6-chloro-4-(methylamino)pyridine-3-carboxylateYield 82%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 0° C. solution of ethyl 4,6-dichloronicotinate (5 g, 22.8 mmol) in MeCN (30 mL) was treated drop-wise with aqueous methylamine (65%, 5.2 g, 45.6 mmol), warmed to RT and stirred for 8 h. The mixture was concentrated to dryness, the residue suspended in H2O and extracted with EtOAc (3×). The combined extracts were washed with brine, dried (MgSO4) and concentrated to give ethyl 6-chloro-4-(methylamino)nicotinate (4 g, 82% yield), which was used in the next step without further purification. 1H NMR (300 MHz, DMSO-d6): δ 8.48 (s, 1H), 8.04 (d, J=4.5 Hz, 1H), 6.71 (s, 1H), 4.27 (q, J=6.9 Hz, 2H), 2.85 (d, J=5.1 Hz, 3H), 1.29 (t, J=6.9 Hz, 3H).

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. extractionextracted with EtOAc (3×)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-72fcc9d71fc6475c9bdf6373ff8881b0
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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