3-(2,3-dichloro-phenoxy)-4-{(1S,3R)-3-ethoxy-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-butylamino}-but-2-enoic acid ethyl ester → HCID 44252314, compound

HRID 19041Notes

Reaction equation

HRID 19041 reaction equation
C(O[C:4](=[O:38])[CH:5]=[C:6]([O:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=1[Cl:37])[CH2:7][NH:8][C@H:9]([C:16](=[O:28])[NH:17][C:18]1[CH:22]=[CH:21][N:20]([CH2:23][C:24]([OH:27])([CH3:26])[CH3:25])[N:19]=1)[CH2:10][C@H:11]([O:13][CH2:14][CH3:15])[CH3:12])C>O1CCCC1>[OH:27][C:24]([CH3:25])([CH3:26])[CH2:23][N:20]1[CH:21]=[CH:22][C:18]([NH:17][C:16](=[O:28])[C@@H:9]([N:8]2[CH2:7][C:6]([O:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=3[Cl:37])=[CH:5][C:4]2=[O:38])[CH2:10][C@H:11]([O:13][CH2:14][CH3:15])[CH3:12])=[N:19]1

Participants

3

Reactant 1

HCID 668990993-(2,3-dichloro-phenoxy)-4-{(1S,3R)-3-ethoxy-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-butylamino}-but-2-enoic acid ethyl ester

Product 1

HCID 44252314HCID 44252314, compoundYield 32.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
160 °C

Procedure

3-(2,3-Dichloro-phenoxy)-4-{(1S,3R)-3-ethoxy-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-butylamino}-but-2-enoic acid ethyl ester (60 mg) was dissolved in tetrahydrofuran (2 mL). The sealed tube was heated in a microwave at 160° C. for 4 h. The resulting solution was concentrated and the residue was purified by reverse phase column chromatography (acetonitrile in water 25% to 100%) to afford (2S,4R)-2-[4-(2,3-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-ethoxy-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (18 mg, 32%): HR-ES-MS m/z calculated for C24H30Cl2N4O5 [M+H]+ 525.1666, observed 525.1669; 1H NMR (300 MHz, CDCl3) δ ppm 1.16 (s, 6H), 1.17-1.27 (m, 6H), 1.84-2.01 (m, 1H), 2.20-2.33 (m, 1H), 3.24-3.40 (m, 1H), 3.49-3.70 (m, 2H), 3.80 (br. s., 1H), 3.95 (s, 2H), 4.27 (d, J=17.8 Hz, 1H), 4.41 (d, J=17.8 Hz, 1H), 4.92 (s, 1H), 5.05 (t, J=7.2 Hz, 1H), 6.69 (d, J=1.9 Hz, 1H), 7.19 (dd, J=8.2, 1.2 Hz, 1H), 7.23-7.27 (m, 1H), 7.31 (d, J=1.9 Hz, 1H), 7.42 (dd, J=8.2, 1.2 Hz, 1H), 8.91 (br. s., 1H).

Workup

  1. concentrationThe resulting solution was concentrated
  2. customthe residue was purified by reverse phase column chromatography (acetonitrile in water 25% to 100%)

Sources & evidence

ORD record
ord-c457f87b6ae94b3d86ec18649956dfbb
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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