Dimethylformamide → racemic 2-(4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)-1-phenylethanol

HRID 595279Notes

Reaction equation

HRID 595279 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:5]=[C:6]([NH:15][C:16]2[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=2)[CH:7]=[C:8]([C:10]2[CH:11]=[N:12][NH:13][CH:14]=2)[CH:9]=1.CN(C=O)C.[CH2:31]1[O:39][CH:32]1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>O>[CH3:3][C:4]1[CH:9]=[C:8]([C:10]2[CH:11]=[N:12][N:13]([CH2:31][CH:32]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[OH:39])[CH:14]=2)[CH:7]=[C:6]([NH:15][C:16]2[N:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=[CH:18][N:17]=2)[CH:5]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7276Styrene OxideHCID 24758Sodium hydrideHCID 118208677N-(3-methyl-5-(1H-pyrazol-4-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 118216537racemic 2-(4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)-1-phenylethanol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

NaH (0.0075 g, 0.19 mmol, 60% dispersion) was added to N-(3-methyl-5-(1H-pyrazol-4-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine (0.02 g, 0.06 mmol) suspended in DMF (1 mL, 0.06 mmol). The reaction mixture was allowed to stir at ambient temperature for 15 minutes. Styrene oxide (0.01 g, 0.08 mmol) was then added. The vial was capped and allowed to stir at 45° C. for 12 hours. H2O (0.2 mL) was added and the reaction was concentrated under reduced pressure. The residue was taken up in DMSO (1.0 mL) and was passed through a syringe filter. The eluent was purified by reverse phase HPLC (0 to 95% ACN/water with 0.1% formic acid modifier) to afford racemic 2-(4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)-1-phenylethanol. MS ESI calcd. for C23H21F3N5O [M+H]+ 440. found 440. 1H NMR (600 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.77 (d, J=4.8, 1H), 7.91 (s, 1H), 7.75 (s, 1H), 7.72 (s, 1H), 7.34-7.27 (m, 5H), 7.25-7.19 (m, 2H), 7.01 (s, 1H), 5.69 (d, J=4.6, 1H), 4.94 (d, J=5.2, 1H), 4.20 (d, J=6.4, 2H), 2.26 (s, 3H).

Workup

  1. customThe vial was capped
  2. stirringto stir at 45° C. for 12 hours
  3. concentrationthe reaction was concentrated under reduced pressure
  4. customwas passed through a syringe
  5. filtrationfilter
  6. customThe eluent was purified by reverse phase HPLC (0 to 95% ACN/water with 0.1% formic acid modifier)

Sources & evidence

ORD record
ord-5e8be7da432d45c5963f560daeb9a68a
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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