Hydrochloric Acid → 6-(Methyloxy)-2-[3-(4-morpholinyl)propanoyl]-1,2,3,4-tetrahydro-7-isoquinolinamine

HRID 1014358Notes

Reaction equation

HRID 1014358 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[N+:13]([O-])=O)[CH2:9][N:8]([C:16](=[O:25])[CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[CH2:7][CH2:6]2.O.O.[Sn](Cl)Cl.Cl.C(=O)(O)[O-].[Na+]>CN(C)C=O.C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[NH2:13])[CH2:9][N:8]([C:16](=[O:25])[CH2:17][CH2:18][N:19]1[CH2:20][CH2:21][O:22][CH2:23][CH2:24]1)[CH2:7][CH2:6]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 61436Stannous chloride dihydrateHCID 516892Sodium BicarbonateHCID 59441881HCID 59441881, compound

Product 1

HCID 594417706-(Methyloxy)-2-[3-(4-morpholinyl)propanoyl]-1,2,3,4-tetrahydro-7-isoquinolinamineYield 68%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

6-(methyloxy)-2-[3-(4-morpholinyl)propanoyl]-7-nitro-1,2,3,4-tetrahydroisoquinoline (assumed 1.62 mmol from previous reaction) was dissolved in dimethylformamide (3.0 mL) and diluted with ethanol (10 mL). The solution was treated with tin (II) chloride dihydrate (2.2 g, 9.6 mmol, Aldrich), hydrochloric acid (1.0 mL, 1.0 mmol, 1 M in water), and stirred for 16 h. Excess saturated aqueous sodium bicarbonate was added carefully and the observed white suspension was stirred for 1 h. The mixture was filtered through celite. The filtrate was concentrated and purified by chromatography on SiO2 (dichloromethane to 20% methanol/dichloromethane) to give 6-(methyloxy)-2-[3-(4-morpholinyl)propanoyl]-1,2,3,4-tetrahydro-7-isoquinolinamine (350 mg, 1.10 mmol, 68% over two steps) which was slightly contaminated with DMF. 1H NMR (400 MHz, DMSO-d6) is complicated by amide rotomers d ppm 2.31-2.41 (m, 4 H), 2.52-2.71 (m, 6 H), 3.50-3.57 (m, 4 H), 3.57-3.62 (m, 2 H), 3.72 (s, 3 H), 4.37-4.47 (two singlets at 4.38 and 4.45, 2 H), 4.54-4.61 (two broad singlets at 4.56 and 4.59, 2 H), 6.38-6.41 (two singlets at 6.39 and 6.40, 1 H), 6.55-6.58 (two singlets at 6.56 and 6.57, 1 H); ESIMS (M+H)+=320.

Workup

  1. stirringthe observed white suspension was stirred for 1 h
  2. filtrationThe mixture was filtered through celite
  3. concentrationThe filtrate was concentrated
  4. custompurified by chromatography on SiO2 (dichloromethane to 20% methanol/dichloromethane)

Sources & evidence

ORD record
ord-3e9a823abe4c43579d344fcd8d849038
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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