Diisopropylethylamine → N-(3-amino-5-isoquinolinyl)-N'-[3-fluoro-4-(trifluoromethyl)benzyl]urea

HRID 586014Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]=[C:10]=[O:11])[CH:5]=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].[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:10]([NH:9][CH2:8][C:6]1[CH:5]=[CH:4][C:3]([C:12]([F:13])([F:14])[F:15])=[C:2]([F:1])[CH:7]=1)=[O:11])[CH:26]=[CH:25][CH:24]=2

Participants

Conditions

Temperature: 80 °C

Procedure

2-Fluoro-4-(isocyanatomethyl)-1-(trifluoromethyl)benzene (2.59 mmol) in toluene (10 mL) was treated with N-(5-amino-3-isoquinolinyl)acetamide (400 mg, 1.99 mmol) and DIEA (1.8 mL). The mixture was heated at 80° C. for 5 hours, cooled to room temperature, and filtered. The solid was triturated with 97:3 CH2Cl2:CH3OH and stirred as a suspension in 48% aqueous HBr (8 mL) at 60° C. for 2 hours. After cooling to room temperature, the mixture was poured into concentrated NH4OH (20 mL). 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 8.81 (s, 1H), 8.68 (s, 1H), 7.94 (s, 1H), 7.76 (t, 1H, J=7.9 Hz), 7.35-7.49 (m, 3H), 7.26 (s, 1H), 7.09 (s, 1H), 6.92 (s, 1H), 6.84 (t, 1H, J=6.0 Hz), 6.62 (s, 1H), 4.41 (d, 2H, J=6.1 Hz).

Workup

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

Sources & evidence

ORD record: ord-e8c4a5e8b7f241d882f81c446225451b
Source dataset: uspto-grants-2005_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06933311B2

Reaction notes

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