1-Methylpyrrolidine → 1-(2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-3-(2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)urea

HRID 1098606Notes

Reaction equation

HRID 1098606 reaction equation
[NH2:1][C:2]1[C:3](=[O:12])[NH:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[F:13][C:14]1[CH:19]=[C:18]([O:20][C:21]2[CH:26]=[CH:25][N:24]=[C:23]([C:27]3[CH:28]=[N:29][N:30]([CH3:32])[CH:31]=3)[CH:22]=2)[CH:17]=[CH:16][C:15]=1[NH:33][C:34](=O)[O:35]C(C)=C.CN1CCCC1>O1CCOCC1.C(OCC)(=O)C>[F:13][C:14]1[CH:19]=[C:18]([O:20][C:21]2[CH:26]=[CH:25][N:24]=[C:23]([C:27]3[CH:28]=[N:29][N:30]([CH3:32])[CH:31]=3)[CH:22]=2)[CH:17]=[CH:16][C:15]=1[NH:33][C:34]([NH:1][C:2]1[C:3](=[O:12])[NH:4][CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=1)=[O:35]

Participants

6

Reactant 3

HCID 84541-MethylpyrrolidineHCID 23157873-Amino-5-(trifluoromethyl)-1,2-dihydropyridin-2-oneHCID 66729122prop-1-en-2-yl 2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenylcarbamate

Product 1

HCID 667291501-(2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-3-(2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)ureaYield 58%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

3-Amino-5-(trifluoromethyl)pyridin-2(1H)-one (44 mg, 0.247 mmol), prop-1-en-2-yl 2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenylcarbamate from Example 21 (85 mg, 0.231 mmol) and N-methylpyrrolidine (7.5 mg, 0.088 mmol) were combined in 1,4-dioxane (0.8 mL). The resultant mixture was heated to 80° C. After 13 h, the mixture was cooled to RT and diluted with ethyl acetate (3 mL). The resultant precipitate was collected by filtration, washed with ethyl acetate and dried in vacuo to provide 1-(2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-3-(2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)urea as an off-white solid (65 mg, 58% yield). 1H NMR (400 MHz, DMSO-d6): δ 12.47 (s, 1 H), 9.56 (s, 1 H), 9.35 (s, 1 H), 8.36 (d, J=5.3 Hz, 1 H), 8.25 (br s, 2 H), 8.17 (t, J=9.4 Hz, 1 H), 7.96 (s, 1 H), 7.59 (s, 1 H), 7.25-7.22 (m, 2 H), 7.00 (d, J=8.5 Hz, 1 H), 6.68 (m, 1 H), 3.84 (s 3 H); MS (ESI) m/z: 489.1 (M+H+).

Workup

  1. filtrationThe resultant precipitate was collected by filtration
  2. washwashed with ethyl acetate
  3. customdried in vacuo

Sources & evidence

ORD record
ord-56106ec04d6f433a8efb8ef169b983cb
Source dataset
uspto-grants-2012_03
Patent number
US08143293B2

Reaction notes

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