Methanol → N-ethyl-2-[(5-methyl-1-phenyl-1,2-dihydro [1,4]oxazino[2,3,4-jk]carbazol-7-yl)oxy]-1-ethanamine

HRID 2415826Notes

Reaction equation

HRID 2415826 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:12]3=[C:13]([O:15][CH2:16][CH:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:11]3[C:10]3[CH:9]=[CH:8][CH:7]=[C:6]([O:24][CH2:25][CH2:26][NH:27][C:28](=O)[CH3:29])[C:5]2=3)[CH:14]=1.CO>C1COCC1>[CH2:28]([NH:27][CH2:26][CH2:25][O:24][C:6]1[C:5]2[C:4]3[C:12]4=[C:13]([O:15][CH2:16][CH:17]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)[N:11]4[C:10]=2[CH:9]=[CH:8][CH:7]=1)[CH:14]=[C:2]([CH3:1])[CH:3]=3)[CH3:29]

Participants

4

Reactant 2

HCID 887MethanolHCID 12148635N-{2-[(5-methyl-1-phenyl-1,2-dihydro[1,4]oxazino[2,3,4-jk]carbazol-7-yl)oxy]ethyl}acetamide

Product 1

HCID 9821559N-ethyl-2-[(5-methyl-1-phenyl-1,2-dihydro [1,4]oxazino[2,3,4-jk]carbazol-7-yl)oxy]-1-ethanamineYield 72.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of N-{2-[(5-methyl-1-phenyl-1,2-dihydro[1,4]oxazino[2,3,4-jk]carbazol-7-yl)oxy]ethyl}acetamide (0.212 g, 0.53 mmol) in THF (10 mL) is added borane-methylsulfide complex (0.15 mL, 1.6 mmol). The mixture is refluxed at 85° C. for 16 hours. After cooling, methanol is slowly added until gas evolution ceased. The solvents are removed under vacuum and methanol (5 mL) is added then removed. The residue is dissolved in CH2Cl2/CH3OH (1:5, 15 mL). Conc. HCl is added and the mixture is heated at 65° C. for 1 h. The mixture is removed from heat, neutralized with aqueous potassium carbonate and then partitioned between water and CH2Cl2 The organic layer is washed with water, dried over magnesium sulfate, and concentrated. Column chromatography (70 g silica gel) using CH3OH/CH2Cl2 (5:95) as eluent gave 0.148 g (70%) of N-ethyl-2-[(5-methyl-1-phenyl-1,2-dihydro[1,4]oxazino[2,3,4-jk]carbazol-7-yl)oxy]-1-ethanamine (TLC: MeOH/CH2Cl2, 5/95, Rf=0.38); conversion to the maleic acid salt and recrystallizing from absolute ethanol gave 0.0223 g of N-ethyl-2-[(5-methyl-1-phenyl-1,2-dihydro[1,4]oxazino[2,3,4-jk]carbazol-7-yl)oxy]-1-ethanamine, maleic acid salt.

Workup

  1. additionis added borane-methylsulfide complex (0.15 mL, 1.6 mmol)
  2. temperatureAfter cooling
  3. customThe solvents are removed under vacuum and methanol (5 mL)
  4. additionis added
  5. customthen removed
  6. dissolutionThe residue is dissolved in CH2Cl2/CH3OH (1:5, 15 mL)
  7. additionConc. HCl is added
  8. temperaturethe mixture is heated at 65° C. for 1 h
  9. customThe mixture is removed
  10. temperaturefrom heat
  11. custompartitioned between water and CH2Cl2 The organic layer
  12. washis washed with water
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-a019081a8f594d63b99d017c056b4d33
Source dataset
uspto-grants-2004_11
Patent number
US06821970B2

Reaction notes

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