tert-Butyl 2-(3-(2,5-Dimethyl-1H-pyrrol-1-yl)-5-(methoxy(methyl)carbamoyl)-1H-pyrazol-1-yl)ethylcarbamate → tert-Butyl 2-(5-Acetyl-3-(2,5-dimethyl-1H-pyrrol-1-yl)-1H-pyrazol-1-yl)ethylcarbamate

HRID 1412003Notes

Reaction equation

HRID 1412003 reaction equation
[CH3:1][C:2]1[N:3]([C:8]2[CH:12]=[C:11]([C:13](=[O:18])N(OC)C)[N:10]([CH2:19][CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[N:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.[CH3:29][Mg+].[Br-]>C1COCC1>[C:13]([C:11]1[N:10]([CH2:19][CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])[N:9]=[C:8]([N:3]2[C:4]([CH3:7])=[CH:5][CH:6]=[C:2]2[CH3:1])[CH:12]=1)(=[O:18])[CH3:29]

Participants

4

Reactant 2

HCID 86684523tert-Butyl 2-(3-(2,5-Dimethyl-1H-pyrrol-1-yl)-5-(methoxy(methyl)carbamoyl)-1H-pyrazol-1-yl)ethylcarbamateHCID 178418689HCID 178418689, compound

Product 1

HCID 86684524tert-Butyl 2-(5-Acetyl-3-(2,5-dimethyl-1H-pyrrol-1-yl)-1H-pyrazol-1-yl)ethylcarbamateYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 250-mL round-bottomed flask equipped with a magnetic stirrer was charged with 287d (7.82 g, 1.0 eq., 20.0 mmol) and THF (100 mL) under N2 protection. A solution of MeMgBr (3.0 M in ether) (17 mL, 2.5 eq., 50.0 mmol) was added at −78° C. The mixture was stirred at room temperature for 3 h and quenched with saturated NH4Cl solution. It was then concentrated under reduced pressure and the residue was extracted with ethyl acetate (3×50 mL). The combined organic layer was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 4:1 petroleum ether/ethyl acetate to afford 287e as colorless oil (5.40 g, 78%). MS-ESI: [M+H]+ 347.0. 1H NMR (500 MHz, CDCl3) δ 6.57 (s, 1H), 5.91 (s, 2H), 4.93 (bs, 1H), 4.71 (t, J=5.5 Hz, 2H), 3.62 (t, J=5.5 Hz, 2H), 2.57 (s, 3H), 2.16 (s, 6H), 1.28 (s, 9H).

Workup

  1. customA 250-mL round-bottomed flask equipped with a magnetic stirrer
  2. customquenched with saturated NH4Cl solution
  3. concentrationIt was then concentrated under reduced pressure
  4. extractionthe residue was extracted with ethyl acetate (3×50 mL)
  5. customThe combined organic layer was evaporated under reduced pressure
  6. customThe residue was purified by silica-gel column chromatography
  7. washeluting with 4:1 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-11418be30cc7411fa85b0b1186e8cc40
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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