Triacetoxyperiodinane → [4-(azetidin-1-yl)-6-chloropyrimidin-5-yl]{1-methyl-5-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazol-4-yl}methanone

HRID 72712Notes

Reaction equation

HRID 72712 reaction equation
[N:1]1([C:5]2[C:10]([CH:11]([C:13]3[CH:14]=[N:15][N:16]([CH3:28])[C:17]=3[C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][N:19]=3)[OH:12])=[C:9]([Cl:29])[N:8]=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[N:1]1([C:5]2[C:10]([C:11]([C:13]3[CH:14]=[N:15][N:16]([CH3:28])[C:17]=3[C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:25])[F:26])=[CH:20][N:19]=3)=[O:12])=[C:9]([Cl:29])[N:8]=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 86712563[4-(azetidin-1-yl)-6-chloropyrimidin-5-yl]{1-methyl-5-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazol-4-yl}methanol

Product 1

HCID 86712564[4-(azetidin-1-yl)-6-chloropyrimidin-5-yl]{1-methyl-5-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazol-4-yl}methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of [4-(azetidin-1-yl)-6-chloropyrimidin-5-yl]{1-methyl-5-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazol-4-yl}methanol (C15) (30 mg, 0.071 mmol) in dichloromethane (3 mL) was cooled to 0° C. and Dess-Martin periodinane (33.1 mg, 0.078 mmol) was added portion-wise. After completion of the addition, the reaction mixture was stirred for 1 hour at 0° C., then warmed to room temperature and stirred for an additional 18 hours. The reaction mixture was diluted with dichloromethane, and then quenched with aqueous sodium bicarbonate solution (1 mL) and aqueous sodium thiosulfate solution (1 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Chromatographic purification using silica gel [Gradient: 0% to 100% (95:2.5:2.5 ethyl acetate/methanol/triethylamine) in heptane] afforded the product. Yield: 29 mg, 0.069 mmol, 97%. LCMS m/z 423.1, 425.2 (M+1). 1H NMR (400 MHz, CD3OD) δ 2.30-2.39 (m, 2H), 3.78 (s, 3H), 3.99-4.07 (m, 4H), 7.89 (d, J=8.2 Hz, 1H), 8.00-8.13 (m, 3H), 8.72 (br s, 1H).

Workup

  1. additionAfter completion of the addition
  2. temperaturewarmed to room temperature
  3. stirringstirred for an additional 18 hours
  4. customquenched with aqueous sodium bicarbonate solution (1 mL) and aqueous sodium thiosulfate solution (1 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customChromatographic purification
  9. customafforded the product

Sources & evidence

ORD record
ord-d86bff1481a045f48d7be14b1f0b18f1
Source dataset
uspto-grants-2014_09
Patent number
US08829010B2

Reaction notes

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