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

HRID 887274Notes

Reaction equation

HRID 887274 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]([CH3:27])[N:21]=[CH:22]2.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[C:12]([F:13])([F:14])[F:15])[CH2:8][NH:9][C:10]([NH:16][C:17]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:18]=1[CH:19]=[C:20]([CH3:27])[N:21]=[CH:22]2)=[O:11]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 122120553-Methylisoquinolin-5-amineHCID 223375622-Fluoro-4-(isocyanatomethyl)-1-(trifluoromethyl)benzene

Product 1

HCID 10362214N-[3-fluoro-4-(trifluoromethyl)benzyl]-N'-(3-methyl-5-isoquinolinyl)urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The product from Example 192A (4.4 mmol) in toluene (10 mL) was treated with 5-amino-3-methylisoquinoline (460 mg, 2.9 mmol) and DIEA (3 mL). The mixture was heated at 80° for 1.5 hours, cooled to room temperature, and filtered. The precipitate thus obtained was purified by silica gel chromatography (97:3 CH2Cl2:CH3OH to 95:5 CH2Cl2:CH3OH) to provide the title compound. The corresponding hydrochloride salt was prepared by treatment with methanolic HCl. 1H NMR (300 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.77 (s, 1H), 8.17 (dd, 1H, J=7.8 Hz, 1.0 Hz), 7.70-7.81 (m, 3H), 7.38-7.53 (m, 3H), 7.19 (t, 1H, 6.1 Hz), 4.47 (d, 2H, J=5.8 Hz), 2.65 (s, 3H); MS (ESI+) m/z 378 (M+H).

Workup

  1. temperatureThe mixture was heated at 80° for 1.5 hours
  2. filtrationfiltered
  3. customThe precipitate thus obtained
  4. customwas purified by silica gel chromatography (97:3 CH2Cl2:CH3OH to 95:5 CH2Cl2:CH3OH)

Sources & evidence

ORD record
ord-08190fdaa402458da988650ad9f9f689
Source dataset
uspto-grants-2012_08
Patent number
US08247413B2

Reaction notes

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