Phosgene → N-(4-isopropylbenzyl)-N'-(3-methyl-5-isoquinolinyl)urea

HRID 586011Notes

Reaction equation

HRID 586011 reaction equation
[CH:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8][NH2:9])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[C:12](Cl)(Cl)=[O:13].CCN(C(C)C)C(C)C.[NH2:25][C:26]1[CH:35]=[CH:34][CH:33]=[C:32]2[C:27]=1[CH:28]=[C:29]([CH3:36])[N:30]=[CH:31]2>C1(C)C=CC=CC=1>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][NH:9][C:12]([NH:25][C:26]2[CH:35]=[CH:34][CH:33]=[C:32]3[C:27]=2[CH:28]=[C:29]([CH3:36])[N:30]=[CH:31]3)=[O:13])=[CH:10][CH:11]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 1382214-IsopropylbenzylamineHCID 122120553-Methylisoquinolin-5-amine

Product 1

HCID 22032671N-(4-isopropylbenzyl)-N'-(3-methyl-5-isoquinolinyl)urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

4-Isopropylbenzylamine (748 mg, 5.02 mmol) in toluene (20 mL) was refluxed with 20% w/v phosgene solution in toluene (3 mL) overnight. The mixture was cooled to room temperature and concentrated in vacuo. The residue was taken up in toluene (20 mL) and was treated with DIEA (4 mL) and 5-amino-3-methylisoquinoline (500 mg, 3.16 mmol). The reaction mixture was stirred was at 80° C. for 6 hours. After cooling to room temperature, a precipitate formed which was collected by filtration and purified by silica gel chromatography (98:2 CH2Cl2:CH3OH) to provide the title compound. The corresponding hydrochloride salt was formed by treatment with methanolic HCl. 1H NMR (300 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.60 (s, 1H), 8.24 (dd, 1H, J=7.5 Hz, 1.0 Hz), 7.74 (s, 1H), 7.68 (d, 1H, J=8.2 Hz), 7.50 (t, 1H, J=8.0 Hz), 7.22-7.30 (m, 4H), 6.99 (t, 1H, 5.6 Hz), 4.32 (d, 2H, J=7.8 Hz), 2.88 (m, 1H), 2.64 (s, 3H), 1.20 (d, 6H, J=6.8 Hz); MS (ESI+) m/z 334 (M+H).

Workup

  1. concentrationconcentrated in vacuo
  2. temperatureAfter cooling to room temperature
  3. customa precipitate formed which
  4. filtrationwas collected by filtration
  5. custompurified by silica gel chromatography (98:2 CH2Cl2:CH3OH)

Sources & evidence

ORD record
ord-c8a6c76255054074b983e802c6f74392
Source dataset
uspto-grants-2005_08
Patent number
US06933311B2

Reaction notes

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