O-Methylhydroxylamine hydrochloride → HCID 74322592, compound

HRID 56352Notes

Reaction equation

HRID 56352 reaction equation
[Br:1][C:2]1[C:3]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)=O)[CH2:12][CH2:11]2)=[O:9])=[N:4][N:5]([CH3:7])[CH:6]=1.Cl.[O:27]([NH2:29])[CH3:28]>C(O)C>[CH3:28][O:27][N:29]=[C:17]([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)[CH2:16][N:13]1[CH2:14][CH2:15][N:10]([C:8]([C:3]2[C:2]([Br:1])=[CH:6][N:5]([CH3:7])[N:4]=2)=[O:9])[CH2:11][CH2:12]1

Participants

4

Reactant 2

HCID 521874O-Methylhydroxylamine hydrochlorideHCID 24810870HCID 24810870, compound

Product 1

HCID 74322592HCID 74322592, compoundYield 23.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

2-(4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)piperazin-1-yl)-1-(4-fluorophenyl)ethanone (100 mg, 0.24 mmol) and methoxylamine hydrochloride (25 mg, 0.31 mmol) were taken up in ethanol (10 mL) in a round-bottom flask and heated to reflux at 90° C. for 21 h. The solvent was removed under reduced pressure and saturated aqueous NaHCO3 (1.5 mL) was added. The mixture was extracted three times with DCM and the organic phase was dried over sodium sulfate, filtered, and concentrated. The crude product was purified by preparative TLC plate (Rf=0.44, 60% EtOAc/Hexane, UV 254 nm) and dried to afford the title compound (25 mg) as a free base. 1H NMR (Acetonitrile-d3, 400 MHz) δ 2.42-2.48 (m, 2H), 2.48-2.54 (m, 2H), 3.35-3.42 (m, 2H), 3.37 (s, 2H), 3.57-3.63 (m, 2H), 3.80 (s, 3H), 3.84 (s, 3H), 7.14 (t, J=8.84 Hz, 2H), 7.60 (dd, J=5.31, 8.84 Hz, 2H), 7.61 (s, 1H). Exact mass calculated for C18H21BrFN5O2: 437.1. Found: LCMS m/z (%)=438.3 (M+H+79Br, 100%), 440.3 (M+H+81Br, 97%).

Workup

  1. temperatureheated
  2. customThe solvent was removed under reduced pressure and saturated aqueous NaHCO3 (1.5 mL)
  3. additionwas added
  4. extractionThe mixture was extracted three times with DCM
  5. dry with materialthe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by preparative TLC plate (Rf=0.44, 60% EtOAc/Hexane, UV 254 nm)
  9. customdried

Sources & evidence

ORD record
ord-fdee6a0adfa14496a8fa11ef31277fd4
Source dataset
uspto-grants-2016_09
Patent number
US09434692B2

Reaction notes

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