Tetrahydrofuran → 6-methoxy-N-((2-chlorothiazole-5-yl)methyl)-N-ethyl-3-chloropyridin-2-amine

HRID 1050718Notes

Reaction equation

HRID 1050718 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]([CH2:11][C:12]2[S:16][C:15]([Cl:17])=[N:14][CH:13]=2)[CH2:9][CH3:10])[C:5]([Cl:18])=[CH:4][CH:3]=1.[O:19]1CCC[CH2:20]1.C[O-].[Na+]>CO>[CH3:20][O:19][C:2]1[N:7]=[C:6]([N:8]([CH2:11][C:12]2[S:16][C:15]([Cl:17])=[N:14][CH:13]=2)[CH2:9][CH3:10])[C:5]([Cl:18])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 10942334Sodium MethoxideHCID 1178764726-chloro-N-((2-chlorothiazole-5-yl)methyl)-N-ethyl-3-chloropyridin-2-amine

Product 1

HCID 1178767126-methoxy-N-((2-chlorothiazole-5-yl)methyl)-N-ethyl-3-chloropyridin-2-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1.5 g of 6-chloro-N-((2-chlorothiazole-5-yl)methyl)-N-ethyl-3-chloropyridine-2-amine, prepared according to the example 11, and 20 mL of tetrahydrofuran were added in a 150 mL single neck flask equipped with a magnetic stirrer, after stirred at room temperature for 10 to 30 minutes, 0.25 g of sodium methoxide in 2.0 mL of methanol were added dropwise. The reaction mixture was stirred at the same temperature overnight, and then extracted with ethyl acetate, the organic layer was separated while the aqueous layer was extracted with ethyl acetate twice. The organic phases were combined, and dried over anhydrous sodium sulfate after washed with an iced aqueous sodium chloride solution twice, then remove the solvent under reduced pressure to obtain 1.20 g of crude product which was purified by a silica gel column chromatography using a petroleum ether/ethyl acetate (15/1) as an eluent to obtain 0.42 g of 6-methoxy-N-((2-chlorothiazole-5-yl)methyl)-N-ethyl-3-chloropyridin-2-amine, having the content of 95.0% as a yellow viscous liquid, GC-MS (M+) (EI: 70 eV, m/z) calc: 317. found: 317. 1H NMR (CDCl3/TMS, 300 MHz) δ (ppm) 1.202 (t, J=7.2 Hz, 3H, CH3), 3.418 (q, J=7.2 Hz, 2H, CH2), 4.033 (s, 3H, CH3), 4.530 (d, J=0.6 Hz, 2H, CH2), 6.726 (d, J=8.1 Hz, 1H, Py H), 7.034 (s, 1H, Thiazole-H), 7.454 (d, J=8.1 Hz, 1H, Py H).

Workup

  1. additionwere added in a 150 mL single neck flask
  2. customequipped with a magnetic stirrer
  3. stirringThe reaction mixture was stirred at the same temperature overnight
  4. extractionextracted with ethyl acetate
  5. customthe organic layer was separated while the aqueous layer
  6. extractionwas extracted with ethyl acetate twice
  7. dry with materialdried over anhydrous sodium sulfate
  8. washafter washed with an iced aqueous sodium chloride solution twice
  9. customremove the solvent under reduced pressure
  10. customto obtain 1.20 g of crude product which
  11. customwas purified by a silica gel column chromatography

Sources & evidence

ORD record
ord-6883f29c648148929881a09107995ed9
Source dataset
uspto-grants-2016_07
Patent number
US09386769B2

Reaction notes

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