1,2-Dichloro-4-(isocyanatomethyl)benzene → N-(3,4-dichlorobenzyl)-N'-(3-methyl-5-isoquinolinyl)urea

HRID 887275Notes

Reaction equation

HRID 887275 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH3:12])[N:6]=[CH:7]2.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][N:21]=[C:22]=[O:23])=[CH:16][C:15]=1[Cl:24]>C1(C)C=CC=CC=1>[Cl:24][C:15]1[CH:16]=[C:17]([CH:18]=[CH:19][C:14]=1[Cl:13])[CH2:20][NH:21][C:22]([NH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH3:12])[N:6]=[CH:7]2)=[O:23]

Participants

4

Reactant 2

HCID 27333681,2-Dichloro-4-(isocyanatomethyl)benzeneHCID 122120553-Methylisoquinolin-5-amine

Product 1

HCID 9998596N-(3,4-dichlorobenzyl)-N'-(3-methyl-5-isoquinolinyl)urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

5-Amino-3-methylisoquinoline (390 mg, 2.47 mmol) and the product from Example 194A (0.36 mL, 2.45 mmol) were heated in toluene (10 mL) at 80° for 2.5 hours. Upon cooling to room temperature, a precipitate formed, which was collected by filtration, washed with toluene, and air-dried. Remaining impurities were removed by slurrying the solid in 9:1 CH2Cl2:CH3OH and then filtering the mixture to provide the title compound. The corresponding hydrochloride salt was formed by treatment of the free base with methanolic HCl. 1H NMR (300 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.27 (s, 1H), 8.17 (dd, 1H, J=7.8 Hz, 1.0 Hz), 7.74 (s, 1H), 7.71 (d, 1H, J=8.1 Hz), 7.61 (m, 2H), 7.50 (t, 1H, J=8.0 Hz), 7.35 (dd, 1H, J=8.3 Hz, 2.2 Hz), 7.12 (t, 1H, 5.9 Hz), 4.37 (d, 2H, J=6.1 Hz), 2.65 (s, 3H); MS (ESI+) m/z 360/362 (M+H, 35Cl/37Cl).

Workup

  1. customa precipitate formed
  2. filtrationwhich was collected by filtration
  3. washwashed with toluene
  4. customair-dried
  5. customRemaining impurities were removed
  6. filtrationCH3OH and then filtering the mixture

Sources & evidence

ORD record
ord-ffe2294bacdc43d8b22371a4e60730da
Source dataset
uspto-grants-2012_08
Patent number
US08247413B2

Reaction notes

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