L-Methionine → 3-(2,5-Dimethyl-pyrrol-1-yl)-5-isopropyl-1-methyl-1H-pyrazole

HRID 450301Notes

Reaction equation

HRID 450301 reaction equation
[CH3:1][C:2]1[N:3]([C:8]2[CH:12]=[C:11]([CH:13]([CH3:15])[CH3:14])[NH:10][N:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.[H-].[Na+].N[C@H:19](C(O)=O)CCSC.[Cl-].[NH4+]>C1COCC1.C(Cl)Cl>[CH3:1][C:2]1[N:3]([C:8]2[N:9]([CH3:19])[N:10]=[C:11]([CH:13]([CH3:15])[CH3:14])[CH:12]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.[CH3:1][C:2]1[N:3]([C:8]2[CH:12]=[C:11]([CH:13]([CH3:15])[CH3:14])[N:10]([CH3:19])[N:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1

Participants

8

Reactant 4

HCID 6137L-MethionineHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 593940413-(2,5-dimethyl-pyrrol-1-yl)-5-isopropyl-1H-pyrazole

Product 2

HCID 674314505-(2,5-Dimethyl-pyrrol-1-yl)-3-isopropyl-1-methyl-1H-pyrazoleYield 29%HCID 674331323-(2,5-Dimethyl-pyrrol-1-yl)-5-isopropyl-1-methyl-1H-pyrazoleYield 63%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(2,5-dimethyl-pyrrol-1-yl)-5-isopropyl-1H-pyrazole (7.7 g, 37.9 mmol) in THF (400 mL) that is purged with nitrogen is added NaH (2.272 g, 56.8 mmol) at 0° C. The mixture is stirred for 10 min in the ice bath then for 10 min at room temperature. Met (4.74 mL, 76 mmol) is added and the mixture is stirred at room temperature for 1 h. At that point the reaction is diluted with DCM and treated with saturated solution of ammonium chloride (10 mL). The mixture is concentrated to dryness and the residue is partitioned in water and DCM. The organic layer is combined, dried over sodium sulfate, concentrated and absorbed onto silica to purify by FCC (0-30% EtOAC/Heptane) to give 5-(2,5-Dimethyl-pyrrol-1-yl)-3-isopropyl-1-methyl-1H-pyrazole (2.4 g, 29%) as the first peak and 3-(2,5-Dimethyl-pyrrol-1-yl)-5-isopropyl-1-methyl-1H-pyrazole (5.24 g, 63%) as the second peak. MS (ESI) m/z 218.3 (m+1).

Workup

  1. concentrationThe mixture is concentrated to dryness
  2. customthe residue is partitioned in water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customabsorbed onto silica
  6. customto purify by FCC (0-30% EtOAC/Heptane)

Sources & evidence

ORD record
ord-0427ccf4efab4d44a180aa2eef4c49a6
Source dataset
uspto-grants-2013_07
Patent number
US08486954B2

Reaction notes

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