Water → HCID 10480618, compound

HRID 1715367Notes

Reaction equation

HRID 1715367 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([CH:14]2[CH2:16][CH2:15]2)=[O:13])=[C:7]2[C:3]=1[CH2:4][N:5]([C@@H:18]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH2:32][CH3:33])[CH:24]=1)[CH2:19][C:20](O)=[O:21])[C:6]2=[O:17].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:47][OH:48].O>O1CCCC1>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([CH:14]2[CH2:15][CH2:16]2)=[O:13])=[C:7]2[C:3]=1[CH2:4][N:5]([C@@H:18]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH2:32][CH3:33])[CH:24]=1)[CH2:19][C:20](=[O:21])[NH:47][OH:48])[C:6]2=[O:17]

Participants

6

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 443297Hydroxyamine hydrochlorideHCID 10457544HCID 10457544, compound

Product 1

HCID 10480618HCID 10480618, compoundYield 87.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3R)-3-[4-chloro-7-(cyclopropanecarbonyl-amino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(3-ethoxy-4-methoxy-phenyl)-propionic acid (1.3 g, 2.8 mmol) in tetrahydrofurane (10 ml) was added carbonyldiimidazole (0.7 g, 4.2 mmol) at room temperature. The solution was stirred for 2 hours at room temperature. To the mixture was added hydroxylamine HCl salt (0.4 g, 5.6 mmol). The resulted mixture was stirred at room temperature for 4 hours. Water (20 ml) was added to the reaction mixture. THF was removed in vacuo and the resulted mixture was added ethyl acetate (30 ml). The mixture was washed with saturated sodium bicarbonate solution (3×20 ml), water (20 ml) and brine (20 ml). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The resulted oil was stirred with ether (5 ml) for 2 hours and filtered to give (1R)-cyclopropanecarboxylic acid {7-chloro-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-hydroxycarbamoyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as white solid (1.2 g, 86%): mp 142-144° C.; 1HNMR (DMSO-d6): δ 0.87-0.89 (m, 4H, c-CH2), 1.28-1.33 (t, J=7.5 Hz, 3H, OCH2CH3), 1.78-1.83 (m, 1H, c-CH), 2.85-2.91 (m, 2H, CH2CO), 3.73 (s, 3H), 4.00 (t, J=7.5 Hz, 2H, OCH2CH3), 4.11 (d, J=17 Hz, 1H, NCHH), 4.60 (d, J=17 Hz, 1H, NCHH), 5.53-5.69 (m, 1H, CHN), 6.92-6.94 (m, 3H, Ar), 7.58 (d, J=10 Hz, 1H, Ar), 8.26 (d, J=10 Hz, 1H, Ar), 8.84 (s, 1H), 10.46 (s, 1H), 10.57 (s, 1H); 13C NMR (DMSO-d6): 8.4, 8.5, 15.2, 15.9, 35.4, 46.2, 52.2, 55.9, 64.3, 74.6, 112.4, 112.7, 119.7, 119.8, 121.5, 131.7, 132.9, 136.4, 140.2, 148.4, 149.1, 166.3, 167.6, 172.4; Anal. Calcd. for C26H28ClN3O7+0.5H2O: C, 58.01; H, 5.48; N, 8.46. Found: C, 57.97; H, 5.29; N, 8.53, H2O, 1.5.

Workup

  1. stirringThe resulted mixture was stirred at room temperature for 4 hours
  2. customTHF was removed in vacuo
  3. additionthe resulted mixture was added ethyl acetate (30 ml)
  4. washThe mixture was washed with saturated sodium bicarbonate solution (3×20 ml), water (20 ml) and brine (20 ml)
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. stirringThe resulted oil was stirred with ether (5 ml) for 2 hours
  9. filtrationfiltered

Sources & evidence

ORD record
ord-19229accf0e042a180526bf083df4332
Source dataset
uspto-grants-2010_09
Patent number
US07799819B2

Reaction notes

Loading…