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

HRID 2056887

Reaction equation

HRID 2056887 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[CH2:5][NH2:6].[C:11](Cl)(Cl)=[O:12].CCN(C(C)C)C(C)C.[NH2:24][C:25]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:26]=1[CH:27]=[C:28]([CH3:35])[N:29]=[CH:30]2>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[CH2:5][NH:6][C:11]([NH:24][C:25]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:26]=1[CH:27]=[C:28]([CH3:35])[N:29]=[CH:30]2)=[O:12]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 66888Benzenemethanamine, 3,4-dimethyl-HCID 81531DiisopropylethylamineHCID 122120553-Methylisoquinolin-5-amine

Product 1

HCID 9996072N-(3,4-dimethylbenzyl)-N'-(3-methyl-5-isoquinolinyl)urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

3,4-Dimethylbenzylamine (0.3 mL, 2.1 mmol) in toluene (11 mL) was added carefully to a 20% w/v solution of phosgene in toluene (4.5 mL). The mixture was refluxed overnight and was then concentrated in vacuo. The residue was then taken up in toluene (10 mL) and treated with DIEA (1.5 mL, 8.63 mmol) and 5-amino-3-methylisoquinoline (155 mg, 1.08 mmol). The reaction mixture was stirred at 80° for 2 h and was then cooled to room temperature. The precipitated solid was collected by filtration and was chromatographed on silica gel (97:3 CH2Cl2—CH3OH to 9:1 CH2Cl2—CH3OH, eluant gradient) to afford the desired product, A-473191. Treatment of this solid with methanolic HCl yielded the corresponding hydrochloride salt. 1H NMR (300 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.59 (s, 1H), 8.24 (d, 1H, J=7.8 Hz), 7.74 (s, 1H), 7.68 (d, 1H, J=8.2 Hz), 7.50 (t, 1H, J=7.9 Hz), 7.08-7.12 (m, 3H), 6.95 (m, 1H), 4.28 (d, 2H, 5.8 Hz), 2.64 (s, 3H), 2.22 (s, 3H), 2.20 (s, 3H); MS (ESI30 ) m/z 320 (M+H).

Workup

  1. temperatureThe mixture was refluxed overnight
  2. concentrationwas then concentrated in vacuo
  3. filtrationThe precipitated solid was collected by filtration
  4. customwas chromatographed on silica gel (97:3 CH2Cl2—CH3OH to 9:1 CH2Cl2—CH3OH, eluant gradient)

Sources & evidence

ORD record
ord-460a3a5b640040d6907e5b3c246cb8ed
Source dataset
uspto-grants-2008_02
Patent number
US07335678B2

Linked notes

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