Potassium Fluoride → HCID 86679987, compound

HRID 1915776Notes

Reaction equation

HRID 1915776 reaction equation
Cl[C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[N:5]=[CH:4][C:3]=1[N+:16]([O-:18])=[O:17].[F-].[K+].[CH3:21][C@@H:22]1[NH:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23]1>CS(C)=O>[CH3:15][O:14][C:11]1[CH:12]=[CH:13][C:8]([CH2:7][N:6]2[C:2]([N:27]3[CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][C@@H:22]3[CH3:21])=[C:3]([N+:16]([O-:18])=[O:17])[CH:4]=[N:5]2)=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 522689Potassium FluorideHCID 7023035(S)-1-Boc-3-methylpiperazineHCID 86679988HCID 86679988, compound

Product 1

HCID 86679987HCID 86679987, compoundYield 88.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-chloro-1-(4-methoxybenzyl)-4-nitro-1H-pyrazole (268 mg, 1.0 mmol) and potassium fluoride (232 mg, 4.0 mmol) in dry DMSO (20 mL) was added (S)-tert-butyl 3-methylpiperazine-1-carboxylate (230 mg, 1.15 mmol) and the mixture heated in the microwave at 100° C. for 8 hr. The mixture was partitioned between water (30 mL) and EtOAc (50 mL) and the organic layer was passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave (S)-tert-butyl 4-(1-(4-methoxybenzyl)-4-nitro-1H-pyrazol-5-yl)-3-methylpiperazine-1-carboxylate as a yellow gum (380 mg). To a solution of this gum (371 mg, 0.86 mmol) in ethanol/water (20 mL/2 mL) was added ammonium chloride (230 mg, 4.3 mmol) and iron powder (192 mg, 3.44 mmol.) and the mixture heated at 80° C. for 1.5 hr. The mixture was cooled, filtered through Celite® and concentrated under reduced pressure. The residue was partitioned between water (30 mL) and DCM (40 mL) and the organic layer was separated, passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-5% MeOH/DCM) gave (S)-tert-butyl 4-(4-amino-1-(4-methoxybenzyl)-1H-pyrazol-5-yl)-3-methylpiperazine-1-carboxylate as a red gum (330 mg, 84% over two steps). 1H NMR (400 MHz, CDCl3) δ 7.17-7.11 (m, 3H), 6.82 (d, J=8.6 Hz, 2H), 5.34 (d, J=14.4 Hz, 1H), 5.17 (d, J=14.4 Hz, 1H), 3.98-3.80 (m, 2H), 3.78 (s, 3H), 3.23 (ddd, J=9.9, 6.4, 3.3 Hz, 1H), 3.01 (td, J=11.4, 3.0 Hz, 1H), 2.92-2.83 (m, 1H), 2.66 (s, 1H), 2.57 (s, 1H), 1.47 (s, 9H), 0.81 (d, J=6.3 Hz, 3H).

Workup

  1. customThe mixture was partitioned between water (30 mL) and EtOAc (50 mL)
  2. customthe organic layer was passed through a phase separation cartridge
  3. concentrationconcentrated under reduced pressure
  4. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-34fba6c007b64e87af2e1b9768720613
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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