1-Hydroxybenzotriazole → (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((S)-2-oxo-oxazolidin-5-ylmethyl)-1H-pyrazol-3-yl]-amide

HRID 19189Notes

Reaction equation

HRID 19189 reaction equation
[OH:1][C:2](C)([CH3:31])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:30])[C@@H:11]([N:16]2[CH2:20][C:19]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])=[CH:18][C:17]2=[O:29])[CH2:12][CH:13]([CH3:15])[CH3:14])=[N:5]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.NC1C=CN(C[C@H]2[O:66][C:65](=O)[NH:64]C2)N=1>ClCCl>[O:66]=[C:65]1[NH:64][CH2:31][C@@H:2]([CH2:3][N:4]2[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:30])[C@@H:11]([N:16]3[CH2:20][C:19]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[Cl:28])=[CH:18][C:17]3=[O:29])[CH2:12][CH:13]([CH3:15])[CH3:14])=[N:5]2)[O:1]1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 44240794(S)-2-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amideHCID 66893932HCID 66893932, compound

Product 1

HCID 57920078(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((S)-2-oxo-oxazolidin-5-ylmethyl)-1H-pyrazol-3-yl]-amideYield 58.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (prepared as in Example 64, 425 mg, 1.30 mmol) in dichloromethane (20 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride salt (275 mg, 1.45 mmol), 1-hydroxybenzotriazole (195 mg, 1.45 mmol) and (S)-5-(3-amino-pyrazol-1-ylmethyl)-oxazolidin-2-one (285 mg, 1.57 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen and then diluted with dichloromethane, washed with 2N hydrochloric acid, saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate. The crude product obtained after concentration, was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g; 0% to 10% methanol/dichloromethane) to afford (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((S)-2-oxo-oxazolidin-5-ylmethyl)-1H-pyrazol-3-yl]-amide (370 mg, 58%) as a white powder: LR-ES-MS m/z calculated for C23H26ClN5O5 [M]+ 487, observed 488 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.4 Hz, 3H), 0.94 (d, J=6.4 Hz, 3H), 1.35-1.50 (m, 1H), 1.50-1.66 (m, 1H), 1.68-1.87 (m, 1H), 3.28 (dd, J=8.8, 6.0 Hz, 1 H), 3.55 (t, J=8.9 Hz, 1H), 4.21 (d, J=18.4 Hz, 1H), 4.27 (d, J=5.1 Hz, 2H), 4.61 (d, J=18.4 Hz, 1H), 4.79 (s, 1H), 4.80-4.95 (m, 2H), 6.47 (d, J=2.1 Hz, 1H), 7.37 (td, J=7.8, 1.2 Hz, 1H), 7.42-7.50 (m, 1H), 7.50-7.57 (m, 2H), 7.61 (d, J=2.1 Hz, 1H), 7.65 (d, J=7.8 Hz, 1H), 10.85 (s, 1H).

Workup

  1. washwashed with 2N hydrochloric acid, saturated sodium bicarbonate solution
  2. dry with materiala saturated sodium chloride solution and dried over magnesium sulfate
  3. customThe crude product obtained
  4. concentrationafter concentration
  5. customwas purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g; 0% to 10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-3fa5f80462d34092bd76684d0f3a979e
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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