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

HRID 2056898
Notes
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Reaction equation

HRID 2056898 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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 1140
Toluene
Solvent
2×

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-03a320bb006c49d59e015b1f05b1e0e8
Source dataset
uspto-grants-2008_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07335678B2

Reaction notes

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