N,N'-Dimethylethylenediamine → methyl 4-{1-hydroxy-1-[1-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-4-yl]ethyl}benzoate

HRID 595300

Reaction equation

HRID 595300 reaction equation
[OH:1][C:2]([C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=1)([C:4]1[CH:5]=[N:6][NH:7][CH:8]=1)[CH3:3].Br[C:20]1[CH:21]=[C:22]([NH:27][C:28]2[N:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][N:29]=2)[CH:23]=[C:24]([CH3:26])[CH:25]=1.CNCCNC.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C.[Cu]I>[OH:1][C:2]([C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=1)([C:4]1[CH:5]=[N:6][N:7]([C:20]2[CH:21]=[C:22]([NH:27][C:28]3[N:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][N:29]=3)[CH:23]=[C:24]([CH3:26])[CH:25]=2)[CH:8]=1)[CH3:3]

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 58456396N-(3-bromo-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amineHCID 118208644methyl 4-[1-hydroxy-1-(1H-pyrazol-4-yl)ethyl]benzoate

Product 1

HCID 118208752methyl 4-{1-hydroxy-1-[1-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-4-yl]ethyl}benzoate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of methyl 4-[1-hydroxy-1-(1H-pyrazol-4-yl)ethyl]benzoate (17 mg, 0.053 mmol), N-(3-bromo-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine (13 mg, 0.053 mmol), copper(I) iodide (1 mg, 0.005 mmol), N1,N2-dimethylethane-1,2-diamine (0.47 mg, 0.005 mmol), and cesium carbonate (52 mg, 0.16 mmol) in 1,4-dioxane (2 mL) was stirred at 130° C. for 50 minutes. After being cooled to room temperature, the mixture was diluted with ethyl acetate and washed with brine. The organic layer was concentrated and the residue was purified by preparative thin layer chromatography to afford methyl 4-{1-hydroxy-1-[1-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-4-yl]ethyl}benzoate. MS ESI calc'd. for C25H23F3N5O3 [M+H]+ 498. found 498. 1H NMR (400 MHz, CDCl3): δ 8.66 (s, 1H), 8.02-8.06 (m, 3H), 7.78 (s, 1H), 7.59-7.63 (m, 3H), 7.51 (s, 1H), 7.18 (s, 1H), 7.06 (s, 1H), 3.92 (s, 3H), 3.79 (s, 1H), 3.49 (s, 1H), 2.41 (s, 3H), 1.97 (s, 3H).

Workup

  1. temperatureAfter being cooled to room temperature
  2. washwashed with brine
  3. concentrationThe organic layer was concentrated
  4. customthe residue was purified by preparative thin layer chromatography

Sources & evidence

ORD record
ord-597e17d7e95e49f48fbef0c8a75fcbae
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Linked notes

Loading…