HCID 66899152, compound → 2-[4-(2-bromo-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamide

HRID 19421Notes

Reaction equation

HRID 19421 reaction equation
C([O:3][C:4](=O)/[CH:5]=[C:6](/[O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[Br:37])\[CH2:7][NH:8][CH:9]([C:17](=[O:29])[NH:18][C:19]1[CH:23]=[CH:22][N:21]([CH2:24][C:25]([OH:28])([CH3:27])[CH3:26])[N:20]=1)[CH2:10][CH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)C>O1CCCC1>[Br:37][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=1[O:30][C:6]1[CH2:7][N:8]([CH:9]([CH2:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:17]([NH:18][C:19]2[CH:23]=[CH:22][N:21]([CH2:24][C:25]([OH:28])([CH3:26])[CH3:27])[N:20]=2)=[O:29])[C:4](=[O:3])[CH:5]=1

Participants

3

Reactant 1

HCID 66899152HCID 66899152, compound

Product 1

HCID 579200522-[4-(2-bromo-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamideYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (E)-3-(2-bromo-phenoxy)-4-{1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-2-(tetrahydro-pyran-4-yl)-ethylamino}-but-2-enoic acid ethyl ester (250 mg) in tetrahydrofuran (8 mL) was placed in an Emrys Optimizer microwave tube and microwaved at 160° C. for 3 h. The mixture was concentrated in vacuo and the residue was purified by ISCO flash chromatography (RediSep silica 4 g, 30% to 100% ethyl acetate/hexanes) which afforded 2-[4-(2-bromo-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamide (80 mg, 35%) as a light yellow solid: HR-ES-MS (m/z) calculated for C25H31BrN4O5 [M+H]+ 547.1551, observed 547.1551. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.04 (br. s., 3H), 1.06 (br. s., 3H), 1.11-1.48 (m, 3H), 1.53-1.73 (m, 3H), 1.73-1.89 (m, 1H), 3.11-3.31 (m, 2H), 3.72-3.87 (m, 2H), 3.89 (s, 2H), 4.24 (d, J=18.4 Hz, 1H), 4.62 (d, J=18.4 Hz, 1H), 4.66-4.72 (m, 1H), 4.79 (s, 1H), 4.93 (dd, J=10.6, 4.8 Hz, 1H), 6.45 (d, J=2.1 Hz, 1H), 7.22-7.34 (m, 1H), 7.48-7.53 (m, 2H), 7.54 (d, J=2.1 Hz, 1H), 7.79 (d, J=8.2 Hz, 1H), 10.81 (br. s., 1H).

Workup

  1. custommicrowaved at 160° C. for 3 h
  2. concentrationThe mixture was concentrated in vacuo
  3. customthe residue was purified by ISCO flash chromatography (RediSep silica 4 g, 30% to 100% ethyl acetate/hexanes) which

Sources & evidence

ORD record
ord-a4d50ff331ea42e9bc50ac26a51cb4a0
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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