Chloroacetone → N-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-yl)-4-methylthiazol-2-amine hydrochloride

HRID 1426168Notes

Reaction equation

HRID 1426168 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([NH:23][C:24]([NH2:26])=[S:25])=[N:11][CH:12]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:28][C:29](=O)[CH3:30].C(N(CC)CC)C>C(O)C>[ClH:22].[CH2:1]([O:8][C:9]1[C:10]([NH:23][C:24]2[S:25][CH:28]=[C:29]([CH3:30])[N:26]=2)=[N:11][CH:12]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6571ChloroacetoneHCID 8471TriethylamineHCID 86639702HCID 86639702, compound

Product 1

HCID 86639701N-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-yl)-4-methylthiazol-2-amine hydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-yl)thiourea (0.280 g, 0.660 mmol), 1-chloropropan-2-one (0.0733 g, 0.792 mmol), triethylamine (0.161 ml, 1.16 mmol), and ethanol (10 mL) was heated at reflux overnight. The reaction mixture was cooled and partitioned between ethyl acetate:ether (1:1) and water. The organic layer was washed with water, brine, dried, and concentrated. The residue was purified via MPLC (Biotage) eluting with 3:1 hexane:ethyl acetate to afford a free base of the title compound as a light yellow oil. The oil was dissolved in ether (6 mL), and 1M HCl in ether (2 mL) was added. The mixture was sonicated to break up the white solid. Hexanes (5 mL) were added, and the mixture was sonicated and filtered. The solids were washed with hexanes and dried to provide 3-(benzyloxy)-5-(2-chlorophenoxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine hydrochloride (0.215 g, 70.7% yield) as a white powder. 1H NMR (DMSO-d6) δ 2.31 (s, 3H), 5.33 (s, 2H), 6.82 (s, 1H), 7.01 (d, 1H), 7.22 (t, 1H), 7.32-7.43 (m, 5H), 7.51-7.62 (m, 5H), 7.67 (d, 1H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. temperatureThe reaction mixture was cooled
  4. custompartitioned between ethyl acetate:ether (1:1) and water
  5. washThe organic layer was washed with water, brine
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was purified via MPLC (Biotage)
  9. washeluting with 3:1 hexane

Sources & evidence

ORD record
ord-96d1a217f03342b69c4f70c1b5bc6a30
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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