1,1'-Carbonyldiimidazole → 3-(7-acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-N-hydroxy-propionamide

HRID 1367082Notes

Reaction equation

HRID 1367082 reaction equation
[C:1]([NH:4][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:13]=1[C:12](=[O:14])[N:11]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:29])[F:28])=[C:22]([O:30][CH2:31][CH3:32])[CH:21]=1)[CH2:16][C:17](O)=[O:18])[CH2:10]2)(=[O:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:46][OH:47]>C1COCC1>[C:1]([NH:4][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:13]=1[C:12](=[O:14])[N:11]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:29])[F:28])=[C:22]([O:30][CH2:31][CH3:32])[CH:21]=1)[CH2:16][C:17]([NH:46][OH:47])=[O:18])[CH2:10]2)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 443297Hydroxyamine hydrochlorideHCID 104788263-(7-Acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid

Product 1

HCID 104120543-(7-acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-N-hydroxy-propionamideYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-(7-Acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-N-hydroxy-propionamide was prepared by the procedure of example 8 from 3-(7-acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid (0.6 g, 1.3 mmol), CDI (0.32 g, 2.0 mmol) and hydroxylamine hydrocloride (0.19 g, 2.6 mmol) in THF (30 ml) to give 3-(7-acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-N-hydroxy-propionamide as white solid (0.22 g, 40% yield): mp 121-123° C.; 1HNMR (DMSO-d6): δ 1.34 (t, J=7.5 Hz, 3H, OCH2CH3), 2.16 (s, 3H, CH3), 2.89 (d, J=7.5 Hz, 2H, CH2), 4.10 (q, J=7.0 Hz, 2H, OCH2CH3), 4.24 (d, J=17.5 Hz, 1H, CH2N), 4.59 (d, J=17.5 Hz, 1H, CH2N), 5.69 (m, 1H, CHN), 6.93 (m, 1H, Ar), 7.03 (t, JH-F=75 Hz, 1H, CF2H), 7.15 (m, 3H, Ar), 7.52 (t, J=7.5 Hz, 1H, Ar), 8.26 (d, J=8 Hz, 1H, Ar), 8.85 (s, 1H, NHOH), 10.26 (s, 1H, NHOH), 10.35 (s, 1H, NHCO). 13CNMR (DMSO-d6): δ14.4, 24.4, 34.5, 51.5, 64.2, 93.9, 113.0, 116.6, 117.3, 117.5, 120.7, 121.3, 122.5, 132.8, 134.0, 137.0, 137.8, 142.2, 149.8, 165.7, 168.0, 168.5; Anal. Calcd. for C22H23F2N3O6+0.13H2O: C, 56.73; H, 5.03; N, 9.02. Found: C, 56.35; H, 4.89; N, 8.75; H2O 0.34.

Sources & evidence

ORD record
ord-b2789cf1722f410fbed97e5ffd7509f4
Source dataset
uspto-grants-2011_02
Patent number
US07893102B2

Reaction notes

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