Hydrochloric Acid → HCID 66603379, compound

HRID 1918483Notes

Reaction equation

HRID 1918483 reaction equation
C(O[CH:4](OCC)[CH2:5][CH2:6][CH2:7][NH2:8])C.[CH:12]([C:14]([CH3:16])=O)=[CH2:13].Cl.Cl.[Br:19][C:20]1[CH:21]=[C:22]([N:26]([CH3:28])N)[CH:23]=[CH:24][CH:25]=1>CCOCC.CCO>[Br:19][C:20]1[CH:25]=[CH:24][C:23]2[C:13]3[CH:4]4[N:8]([CH2:7][CH2:6][CH2:5]4)[CH2:16][CH2:14][C:12]=3[N:26]([CH3:28])[C:22]=2[CH:21]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 6570Methyl vinyl ketoneHCID 806724,4-DiethoxybutylamineHCID 53401180HCID 53401180, compound

Product 1

HCID 66603379HCID 66603379, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-aminobutyraldehyde diethyl acetal (12.5 mL, 63.3 mmol) in Et2O (25 mL) was added methyl vinyl ketone (6.70 mL, 82.3 mmol). After 1 h, concentrated HCl (35 mL) was added, and the reaction mixture was heated at 100° C. for 3 h. After the mixture was concentrated, the residue was diluted with EtOH (25 mL), and 1-(3-bromophenyl)-1-methylhydrazine hydrochloride (3.90 g, 15.9 mmol) was added followed by concentrated HCl (25 mL). The reaction was heated at reflux overnight. After the mixture was concentrated, the residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give 9-bromo-7-methyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole (0.95 g, 39%) as an orange solid. 9-Bromo-7-methyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole (0.15 g, 0.49 mmol) was reacted according to the procedure of Example 2 (step b) to give a yellow oil in 20% (46 mg). The yellow oil was dissolved in CH3OH (1 mL) and was treated with 2 N HCl in Et2O (1 mL). The resulting solid was isolated by filtration and dried under vacuum to give the title compound (49 mg, 99%) as a yellow powder: mp 235-240° C.; 1H NMR (500 MHz, CD3OD) δ 9.10 (d, J=2.0 Hz, 1H), 8.41 (dd, J=8.5, 2.5 Hz, 1H), 7.97 (d, J=8.0 Hz, 1H), 7.85 (d, J=7.5 Hz, 1H), 7.66 (d, J=8.5 Hz, 1H), 7.59 (d, J=2.0 Hz, 1H), 7.16 (dd, J=8.5, 2.0 Hz, 1H), 7.03 (d, J=1.5 Hz, 1H), 6.89 (dd, J=7.0, 2.0 Hz, 1H), 5.15 (t, J=7.0 Hz, 1H), 3.77 (s, 3H), 3.77-3.71 (m, 4H), 3.49-3.44 (m, 1H), 3.28-3.25 (m, 1H), 2.76-2.72 (m, 1H), 2.31-2.19 (m, 3H); ESI MS m/z 465 [M+H]+; HPLC (Method A) 97.2% (AUC), tR=12.8 min.

Workup

  1. concentrationAfter the mixture was concentrated
  2. additionwas added
  3. temperatureThe reaction was heated
  4. temperatureat reflux overnight
  5. concentrationAfter the mixture was concentrated
  6. customthe residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-4d5affe1612c411da2014b829b1413b4
Source dataset
uspto-grants-2013_12
Patent number
US08618299B2

Reaction notes

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