Diisopropylethylamine → N-(3-amino-5-isoquinolinyl)-N'-{1-[4-(trifluoromethyl)phenyl]ethyl}urea

HRID 586013Notes

Reaction equation

[N:1]([CH:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=1)[CH3:5])=[C:2]=[O:3].[NH2:16][C:17]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:18]=1[CH:19]=[C:20]([NH:27]C(=O)C)[N:21]=[CH:22]2.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[NH2:27][C:20]1[N:21]=[CH:22][C:23]2[C:18]([CH:19]=1)=[C:17]([NH:16][C:2]([NH:1][CH:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:13])([F:14])[F:15])=[CH:8][CH:7]=1)[CH3:5])=[O:3])[CH:26]=[CH:25][CH:24]=2

Participants

Conditions

Temperature: 80 °C

Procedure

1-(1-Isocyanatoethyl)-4-(trifluoromethyl)benzene (1.64 mmol) in toluene (8 mL) was treated with N-(5-amino-3-isoquinolinyl)acetamide (220 mg, 1.09 mmol) and DIEA (1.4 mL). The mixture was heated at 80° C. for 6 hours, cooled to room temperature, and the precipitate was collected by filtration. The solid was triturated with 97:3 CH2Cl2:CH3OH and stirred as a suspension in 48% aqueous HBr (8 mL) at 60° C. for 4 hours. After cooling to room temperature, the mixture was poured into concentrated NH4OH (20 mL) and filtered. The solid was washed with water and air-dried to provide the title compound. The corresponding hydrochloride salt was prepared by treatment with methanolic HCl. 1H NMR (300 MHz, DMSO-d6) δ 9.05 (s, 1H), 8.64 (s, 1H), 7.91 (d, 1H), 7.58-7.74 (m, 4H), 7.22-7.36 (m, 3H), 7.14-7.18 (m, 2H), 6.97 (s, 1H), 4.94 (m, 1H), 1.44 (d, 3H, J=6.8 Hz); MS (ESI+) m/z 375 (M+H).

Workup

temperaturecooled to room temperature
filtrationthe precipitate was collected by filtration
customThe solid was triturated with 97:3 CH2Cl2
temperatureAfter cooling to room temperature
additionthe mixture was poured into concentrated NH4OH (20 mL)
filtrationfiltered
washThe solid was washed with water
customair-dried

Sources & evidence

ORD record: ord-49b98e5ad0ba4e7fab6ceb8d313a9a64
Source dataset: uspto-grants-2005_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06933311B2

Reaction notes

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