Diisopropylethylamine → 2,3-Dihydro-2-[2-[[(4-methoxyphenyl)methyl]methylamino]ethyl]-4-methylpyrido[3,2-f]-1,4-oxazepine-5(4H)-thione

HRID 247347

Reaction equation

HRID 247347 reaction equation
Cl[CH2:2][CH2:3][CH:4]1[CH2:10][N:9]([CH3:11])[C:8](=[S:12])[C:7]2[CH:13]=[CH:14][CH:15]=[N:16][C:6]=2[O:5]1.[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][NH:26][CH3:27])=[CH:21][CH:20]=1.C(N(C(C)C)CC)(C)C>C(O)C>[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][N:26]([CH3:27])[CH2:2][CH2:3][CH:4]2[CH2:10][N:9]([CH3:11])[C:8](=[S:12])[C:7]3[CH:13]=[CH:14][CH:15]=[N:16][C:6]=3[O:5]2)=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 4854071-(4-methoxyphenyl)-N-methylmethanamine4×HCID 137264422-(chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepine-5(4H)thione

Product 1

HCID 140984902,3-Dihydro-2-[2-[[(4-methoxyphenyl)methyl]methylamino]ethyl]-4-methylpyrido[3,2-f]-1,4-oxazepine-5(4H)-thione

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To 40 ml of absolute ethanol was added 5.0 g (0.0194 mole) of 2-(2-chloroethyl-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepine-5(4H)-thione, 3.53 g (0.021 mole) of 4-methoxy-N-methylbenzenemethanamine and 2.75 g (0.021 mole) of diisopropylethylamine and the reaction solution heated to reflux for 18 hr. Another 1.0 g (0.006 mole) of 4-methoxy-N-methylbenzenemethanamine was added and heating continued for 4 hr. An additional 1.0 g (0.006 mole) of 4-methoxy-N-methylbenzenemethanamine was added and heating continued overnight. Still an additional 0.6 g (0.0036 mole) of 4-methoxy-N-methylbenzenemethanamine was added and heating continued for 24 hr. The ethanol was removed by rotary evaporation. The residue was taken up in 100 ml of methylene chloride and treated with ~8 ml of acetic anhydride overnight. The methylene chloride was extracted with 3×100 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 2×100 ml of chloroform, cooled, basified with concentrated sodium hydroxide, and extracted into 3×100 ml of chloroform. The combined organic extracts were dried over sodium sulfate, filtered, concentrated by rotary evaporation, and triturated with isopropyl ether. Because the crystals were still impure, they were dissolved in 100 ml of methylene chloride, washed with 2×50 ml of 4N sodium hydroxide, dried over sodium sulfate, filtered, and concentrated by rotary evaporation. The residue was crystallized from isopropyl alcohol to give 4 g (56%) of yellow analytically pure crystals, m.p. 128°-30° C.

Workup

  1. temperaturethe reaction solution heated
  2. temperatureto reflux for 18 hr
  3. temperatureheating
  4. temperatureheating continued overnight
  5. temperatureheating
  6. waitcontinued for 24 hr
  7. customThe ethanol was removed by rotary evaporation
  8. additiontreated with ~8 ml of acetic anhydride overnight
  9. extractionThe methylene chloride was extracted with 3×100 ml of 1N hydrochloric acid
  10. washThe combined aqueous extracts were washed with 2×100 ml of chloroform
  11. temperaturecooled
  12. extractionextracted into 3×100 ml of chloroform
  13. dry with materialThe combined organic extracts were dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated by rotary evaporation
  16. customtriturated with isopropyl ether
  17. dissolutionthey were dissolved in 100 ml of methylene chloride
  18. washwashed with 2×50 ml of 4N sodium hydroxide
  19. dry with materialdried over sodium sulfate
  20. filtrationfiltered
  21. concentrationconcentrated by rotary evaporation
  22. customThe residue was crystallized from isopropyl alcohol
  23. customto give 4 g (56%) of yellow analytically pure crystals, m.p. 128°-30° C.

Sources & evidence

ORD record
ord-8143fa6122c84bc3b7a694d08765e7a1
Source dataset
uspto-grants-1987_11
Patent number
US04705853

Linked notes

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