Isoquinoline → (3-{[1-(3-Methoxy-phenyl)-ethyl]-methyl-amino}-propyl)-carbamic acid ter-butyl ester

HRID 969292Notes

Reaction equation

HRID 969292 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]([NH:11][CH3:12])[CH3:10])[CH:6]=[CH:7][CH:8]=1.C1[C:22]2[C:17](=[CH:18]C=CC=2)[CH:16]=CN=1.Cl[CH2:24][CH2:25][CH2:26][NH:27][C:28](=[O:30])[OH:29].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:17]([O:29][C:28](=[O:30])[NH:27][CH2:26][CH2:25][CH2:24][N:11]([CH:9]([C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)[CH3:10])[CH3:12])([CH3:22])([CH3:18])[CH3:16]

Participants

6

Reactant 4

HCID 8405IsoquinolineHCID 11430Potassium CarbonateHCID 148716881-(3-Methoxyphenyl)-N-methylethanamineHCID 17868818N-(3-chloropropyl)carbamic acid

Product 1

HCID 56930479(3-{[1-(3-Methoxy-phenyl)-ethyl]-methyl-amino}-propyl)-carbamic acid ter-butyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of [1-(3-methoxy-phenyl)-ethyl]-methyl-amine (IV) (Grethe, Guenter; Lee, Hsi Lin; Uskokovic, Milan; Brossi, Arnold. Syntheses in the isoquinoline series. Synthesis of 2,3-dihydro-4(1H)-isoquinolones. Journal of Organic Chemistr 1968, 33, 491-494) (320 mg, 1.9 mmol), (3-chloro-propyl)-carbamic acid tert-butylic ester (370 mg, 1.9 mmol), K2CO3 (260 mg, 1.9 mmol) and a catalytic quantity of KI in DMF (5 mL) was stirred under reflux conditions for 24 h. Evaporation of the solvent afforded a residue which was purified by gravity column. Elution with CHCl3/MeOH/aqueous 30% ammonia solution (9:1:0.005) afforded V as an oil: 40% yield, 1H NMR (200 MHz, CDCl3) δ 7.20 (t, J=8.0 Hz, 1H); 6.74-6.95 (m, 3H), 5.38 (br s, 1H, exchangeable with D2O), 3.80 (s, 3H); 3.50 (q, J=7.0 Hz, 1H), 3.13 (q, J=6.2 Hz, 2H), 2.30-2.52 (m, 2H), 2.19 (s, 3H), 1.54-1.68 (m, 2H), 1.44 (s, 9H), 1.35 (d, J=6.6 Hz, 3).

Workup

  1. customEvaporation of the solvent
  2. customafforded a residue which
  3. customwas purified by gravity column
  4. washElution with CHCl3/MeOH/aqueous 30% ammonia solution (9:1:0.005)
  5. customafforded V as an oil

Sources & evidence

ORD record
ord-3bbb910f82654942a5fac4d3d24b6709
Source dataset
uspto-grants-2007_12
Patent number
US07307083B2

Reaction notes

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