Water → 2-methyl-3-(4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)propane-1,2-diol

HRID 595305Notes

Reaction equation

HRID 595305 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][N:19]=2)[CH:5]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH2:13][C:14]([CH3:16])=[CH2:15])[CH:12]=2)[CH:7]=1.C[N+]1([O-])CC[O:32]CC1.C1COCC1.[OH2:41]>[Os](=O)(=O)(=O)=O>[CH3:15][C:14]([OH:32])([CH2:13][N:11]1[CH:12]=[C:8]([C:6]2[CH:5]=[C:4]([NH:17][C:18]3[N:23]=[C:22]([C:24]([F:26])([F:25])[F:27])[CH:21]=[CH:20][N:19]=3)[CH:3]=[C:2]([CH3:1])[CH:7]=2)[CH:9]=[N:10]1)[CH2:16][OH:41]

Participants

6

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 82029Methyl morpholine oxideHCID 118208710N-(3-methyl-5-(1-(2-methylallyl)-1H-pyrazol-4-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 1182085542-methyl-3-(4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)propane-1,2-diol

Reagents, catalysts & solvents 1

HCID 30318Osmium TetroxideCatalyst

Procedure

Osmium tetroxide (290 μl, 0.04 mmol) was added to a flask containing N-(3-methyl-5-(1-(2-methylallyl)-1H-pyrazol-4-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine (56 mg, 0.15 mmol), N-methylmorpholine N-oxide (26.4 mg, 0.225 mmol), THF (1000 μL) and water (500 μL). The reaction mixture was stirred at room temperature for 3.5 hours. Silica was added and the mixture concentrated under reduced pressure. The residue was purified by column chromatography on silica (0-10% MeOH/DCM) and concentrated under reduced pressure. The racemic mixture was purified by chiral SFC (IA column, 40% MeOH with 0.25% DMEA/CO2) to afford 2-methyl-3-(4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)propane-1,2-diol (Example 21.1, Isomer 1, early eluting): MS ESI calcd. for C19H21F3N5O2 [M+H]+ 408. found 408, 1H NMR δ ppm (DMSO-d6): 10.11 (1H, s), 8.80 (1H, d, J=4.88 Hz), 7.95 (1H, s), 7.81 (1H, s), 7.73 (1H, s), 7.33 (1H, s), 7.24 (1H, d, J=4.88 Hz), 7.05 (1H, s), 4.80 (1H, t, J=5.61 Hz), 4.67 (1H, s), 4.11 (1H, d, J=13.94 Hz), 4.05 (1H, d, J=13.90 Hz), 3.18-3.20 (2H, m), 2.29 (3H, s), 0.95 (3H, s), and 2-methyl-3-(4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)propane-1,2-diol (Example 21.2, Isomer 2, late eluting): MS ESI calcd. for C19H21F3N5O2 [M+H]+ 408. found 408, 1H NMR δ ppm (DMSO-d6): 10.11 (1H, s), 8.80 (1H, d, J=4.88 Hz), 7.95 (1H, s), 7.81 (1H, s), 7.73 (1H, s), 7.33 (1H, s), 7.24 (1H, d, J=4.88 Hz), 7.05 (1H, s), 4.80 (1H, t, J=5.61 Hz), 4.67 (1H, s), 4.11 (1H, d, J=13.94 Hz), 4.05 (1H, d, J=13.90 Hz), 3.18-3.20 (2H, m), 2.29 (3H, s), 0.95 (3H, s).

Workup

  1. additionSilica was added
  2. concentrationthe mixture concentrated under reduced pressure
  3. customThe residue was purified by column chromatography on silica (0-10% MeOH/DCM)
  4. concentrationconcentrated under reduced pressure
  5. customThe racemic mixture was purified by chiral SFC (IA column, 40% MeOH with 0.25% DMEA/CO2)

Sources & evidence

ORD record
ord-84d4e28a6a4d4d539478f8a1bd70e474
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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