Sodium Carbonate → Ethyl 6-(methoxymethylamino)-4-[(1-methylethyl)amino]-3-pyridinecarboxylate

HRID 599333Notes

Reaction equation

HRID 599333 reaction equation
Cl[C:2]1[CH:12]=[C:11]([NH:13][CH:14]([CH3:16])[CH3:15])[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=1.Cl.[CH3:18][O:19][NH:20][CH3:21].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[CH:14]([NH:13][C:11]1[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=[C:2]([N:20]([O:19][CH3:18])[CH3:21])[CH:12]=1)([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 86629464HCID 86629464, compound

Product 1

HCID 86629463Ethyl 6-(methoxymethylamino)-4-[(1-methylethyl)amino]-3-pyridinecarboxylateYield 97%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of ethyl 6-chloro-4-(isopropylamino)nicotinate (3.0 g, 12.4 mmol), O,N-dimethylhydroxylamine hydrochloride (35.0 g, 0.35 mol) in dioxane (10 mL) was heated at 180° C. for 6 h. After cooling to RT, the reaction mixture was neutralized with saturated Na2CO3 solution to pH 7-8. The aqueous mixture was concentrated under reduced pressure and was extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried (MgSO4) and concentrated to give ethyl 4-(isopropylamino)-6-(methoxy(methyl)amino)nicotinate (3.2 g, 97% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.48 (s, 1 H), 7.82 (d, J=7.2 Hz, 1 H), 6.10 (s, 1 H), 4.22 (q, J=7.2 Hz, 2 H), 3.77 (m, 4H), 3.18 (s, 3 H), 1.27 (t, J=7.2 Hz, 3 H), 1.20 (d, J=6.4 Hz, 6 H).

Workup

  1. temperatureAfter cooling to RT
  2. concentrationThe aqueous mixture was concentrated under reduced pressure
  3. extractionwas extracted with EtOAc (3×100 mL)
  4. washThe combined organics were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-3b30627efd734a7dab9fe8794f8c71f9
Source dataset
uspto-grants-2011_03
Patent number
US07897762B2

Reaction notes

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