1,2-Dichloroethane → 6-(2-Oxo-oxazolidin-3-yl)-hexanoic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1h-isoindol-5-yl-methyl]-amide

HRID 331542Notes

Reaction equation

HRID 331542 reaction equation
C1CCN2C(=NCCC2)CC1.Cl.[NH2:13][CH2:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[C:20](=[O:24])[N:19]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:18]2=[O:33].[O:34]=[C:35]1[N:39]([CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][C:45](O)=[O:46])[CH2:38][CH2:37][O:36]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(#N)C>[O:32]=[C:26]1[CH:25]([N:19]2[C:18](=[O:33])[C:17]3[C:21](=[CH:22][CH:23]=[C:15]([CH2:14][NH:13][C:45](=[O:46])[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40][N:39]4[CH2:38][CH2:37][O:36][C:35]4=[O:34])[CH:16]=3)[C:20]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 43166890HCID 43166890, compoundHCID 670197065-(Aminomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione hydrochloride

Product 1

HCID 577305006-(2-Oxo-oxazolidin-3-yl)-hexanoic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1h-isoindol-5-yl-methyl]-amideYield 42%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

DBU (1.2 g, 8.1 mmol) was added to a stirred suspension of 5-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (1.0 g, 3.1 mmol) in acetonitrile (35 mL), resulting in the formation of a clear solution. The mixture was stirred at room temperature for 10 minutes, and then, 6-(2-oxo-oxazolidin-3-yl)-hexanoic acid (2.0 g, 10 mmol) and HOBt (0.5 g, 3.7 mmol) were added, followed by EDC (0.89 g, 4.7 mmol). After stirring for an additional 16 hours, the mixture was evaporated under vacuum. The residue was partitioned between ethyl acetate (50 mL) and water (100 mL), and the aqueous phase was extracted with ethyl acetate (3×50 mL). The combined organic layers were evaporated. The residue was chromatographed on silica, using a methylene chloride-methanol gradient, eluting 0.61 g of the product at 93:7 methylene chloride-methanol, in 42% yield; mp 178-180° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 25/75 CH3CN/0.1% H3PO4, 3.36 (98.33%); 1H NMR (DMSO-d6) δ 1.26-1.28 (m, 2H), 1.43-1.61 (m, 4H), 2.04-2.08 (m, 1H), 2.18 (t, J=7.4 Hz, 2H), 2.46-2.63 (m, 2H), 2.83-2.96 (m, 1H), 3.12 (t, J=7.1 Hz, 2H), 3.49 (t, J=8.0 Hz, 2H), 4.42 (t, J=8.0 Hz, 2H), 4.43 (d, J=5.8 Hz, 2H), 5.15 (dd, J=12.9 Hz, J=5.4 Hz, 1H), 7.72-7.77 (m, 2H), 7.89 (d, J=7.8 Hz, 1H), 8.51 (t, J=5.8 Hz, 1H), 11.12 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 24.8, 25.7, 26.4, 30.9, 35.1, 41.9, 43.3, 43.8, 49.0, 61.5, 121.8, 123.5, 129.7, 131.6, 133.3, 147.8, 157.8, 167.0, 167.1, 169.8, 172.4, 172.7; Anal. Calcd for C23H26N4O7+0.3H2O: C, 58.05; H, 5.63; N, 11.77. Found: C, 58.05; H, 5.42; N, 11.62.

Workup

  1. customresulting in the formation of a clear solution
  2. stirringAfter stirring for an additional 16 hours
  3. customthe mixture was evaporated under vacuum
  4. customThe residue was partitioned between ethyl acetate (50 mL) and water (100 mL)
  5. extractionthe aqueous phase was extracted with ethyl acetate (3×50 mL)
  6. customThe combined organic layers were evaporated
  7. customThe residue was chromatographed on silica
  8. washeluting 0.61 g of the product at 93:7 methylene chloride-methanol

Sources & evidence

ORD record
ord-d6485ec5537f4625976c137f417faeb4
Source dataset
uspto-grants-2014_11
Patent number
US08877780B2

Reaction notes

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