1,1'-Carbonyldiimidazole → HCID 10097051, compound

HRID 1367079Notes

Reaction equation

HRID 1367079 reaction equation
[CH:1]1([C:4]([NH:6][C:7]2[CH:8]=[CH:9][CH:10]=[C:11]3[C:15]=2[C:14](=[O:16])[N:13]([CH:17]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH:29]([F:31])[F:30])=[C:24]([O:32][CH2:33][CH3:34])[CH:23]=2)[CH2:18][C:19](O)=[O:20])[CH2:12]3)=[O:5])[CH2:3][CH2:2]1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:48][OH:49]>C1COCC1>[F:30][CH:29]([F:31])[O:28][C:25]1[CH:26]=[CH:27][C:22]([CH:17]([N:13]2[C:14](=[O:16])[C:15]3[C:11](=[CH:10][CH:9]=[CH:8][C:7]=3[NH:6][C:4]([CH:1]3[CH2:3][CH2:2]3)=[O:5])[CH2:12]2)[CH2:18][C:19](=[O:20])[NH:48][OH:49])=[CH:23][C:24]=1[O:32][CH2:33][CH3:34]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 443297Hydroxyamine hydrochlorideHCID 10027851HCID 10027851, compound

Product 1

HCID 10097051HCID 10097051, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Cyclopropanecarboxylic acid {2-[1-(4-difluoromethoxy-3-ethoxy-phenyl)-2-hydroxycarbamoyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide was prepared by the procedure of example 8 from 3-[7-(cyclopropanecarbonyl-amino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid (0.8 g, 1.7 mmol), CDI (0.41 g, 2.5 mmol) and hydroxylamine hydrochloride (0.23 g, 3.6 mmol) in THF (30 ml) to give cyclopropanecarboxylic acid {2-[1-(4-difluoromethoxy-3-ethoxy-phenyl)-2-hydroxycarbamoyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as white solid (0.60 g, 80% yield): mp 116-118° C.; 1HNMR (CDCl3): δ 0.82 (m, 2H, c-CH2), 1.02 (m, 2H, c-CH2), 1.36 (t, J=6.8 Hz, 3H, OCH2CH3), 1.58 (m, 1H, c-CH, 2.86 (dd, J=5, 15 Hz, 1H, CH2), 3.15 (dd, J=10, 15 Hz, 1H, CH2), 3.30 (broad, 1H, NHOH, 4.01 (q, J=7.0 Hz, 2H, OCH2CH3), 4.02 (d, J=17.5 Hz, 1H, CH2N), 4.34 (d, J=17.5 Hz, 1H, CH2N), 5.42 (broad, 1H, NH2), 5.71 (m, 1H, CHN), 6.07 (broad, 1H, NHOH), 6.53 (t, JH-F=75 Hz, 1H, CF2H), 6.88 (m, 3H, Ar), 7.07 (d, J=7.5 Hz, 1H, Ar), 7.30 (t, J=7.5 Hz, 1H, Ar), 8.28 (d, J=8 Hz, 1H, Ar), 10.35 (s, 1H, NHCO). 13CNMR (CDCl3): δ 8.27, 8.39, 14.5, 16.0, 35.4, 47.3, 52.4, 64.8, 111.8, 113.3, 115.9, 116.9, 117.0, 118.9, 120.0, 122.6, 133.3, 136.6, 137.6, 140.0, 141.5, 150.8, 167.5, 169.7, 172.8; Anal. Calcd. for C24H25F2N3O6+0.34H2O: C, 58.16; H, 5.22; N, 8.48. Found: C, 58.25; H, 5.37; N, 8.58, 1.25H2O

Sources & evidence

ORD record
ord-482534f7f4884a5ea82673dcc167bf26
Source dataset
uspto-grants-2011_02
Patent number
US07893102B2

Reaction notes

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