Water → HCID 10254197, compound

HRID 1715365Notes

Reaction equation

HRID 1715365 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)([N:36]1C=CN=C1)=O.[NH4+].[OH-].O>C1COCC1>[C:20]([CH2:19][C@@H:18]([N:5]1[C:6](=[O:17])[C:7]2[C:3](=[C:2]([Cl:1])[CH:10]=[CH:9][C:8]=2[NH:11][C:12]([CH:14]2[CH2:16][CH2:15]2)=[O:13])[CH2:4]1)[C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH2:32][CH3:33])[CH:24]=1)(=[O:21])[NH2:36]

Participants

6

Reactant 4

HCID 962WaterHCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 10457544HCID 10457544, compound

Product 1

HCID 10254197HCID 10254197, compoundYield 82%

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 (0.62 g, 1.3 mmol) in THF (5 ml) was added carbonyldiimidazole (0.3 g, 2 mmol) at room temperature. The solution was stirred for 2 hrs at room temperature. To the mixture was added NH4OH (13.8 N, 0.3 ml, 3.9 mmol). The resulting mixture was stirred at room temperature for 4 hrs. Water (20 ml) was added to the reaction mixture. THF was removed in vacuo and to the resulting 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 resulting oil was stirred with ether (5 ml) for 2 hrs and filtered to give (1R)-cyclopropanecarboxylic acid {2-[2-carbamoyl-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-7-chloro-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as white solid (0.5 g, 82%): mp 201-203° C.; 1HNMR (CDCl3): δ 0.88-0.91 (m, 2H, c-CH2), 1.08-1.11 (m, 2H, c-CH2), 1.45 (t, J=7.5 Hz, 3H, OCH2CH3), 1.65-1.68 (m, 1H, c-CH), 2.98 (dd, J=5, 16 Hz, 1H, CHH), 3.36 (dd, J=5, 16 Hz, 1H, CHH), 3.86 (s, 3H, OCH3), 4.08 (q, J=7.5 Hz, 2H, OCH2CH3), 4.13 (d, J=17 Hz, 1H, NCHH), 4.35 (d, J=17 Hz, 1H, NCHH), 5.42 (broad s, 1H), 5.58-5.64 (m, 1H, CHN), 6.00 (broad s, 1H), 6.83-6.95 (m, 3H, Ar), 7.36 (d, J=9 Hz, 1H, Ar), 8.43 (d, J=9 Hz, 1H, Ar), 10.41 (s, 1H); 13C NMR (CDCl3): 8.4, 14.7, 16.1, 38.6, 48.6, 46.7, 53.2, 53.4, 56.0, 64.5, 65.8, 112.2, 119.0, 119.1, 119.5, 121.8, 130.6, 132.8, 136.6, 139.1, 148.7, 149.4, 169.0, 171.8, 172.6; Anal. Calcd. for C24H26ClN3O5: C, 61.08; H, 5.55; N, 8.90. Found: C, 60.89; H, 5.42; N, 8.51.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 4 hrs
  2. customTHF was removed in vacuo and to the resulting mixture
  3. additionwas 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 resulting oil was stirred with ether (5 ml) for 2 hrs
  9. filtrationfiltered

Sources & evidence

ORD record
ord-f9fb29420362459281f505838cb84b2e
Source dataset
uspto-grants-2010_09
Patent number
US07799819B2

Reaction notes

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