Water → HCID 66589506, compound

HRID 1091329Notes

Reaction equation

HRID 1091329 reaction equation
CS(O)(=O)=O.[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=O)[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2.C1N=CN([C:31](N2C=NC=C2)=[O:32])C=1.[NH:38]1[CH:42]=[CH:41][N:40]=[C:39]1[C:43]1[CH:48]=[CH:47][C:46]([NH2:49])=[CH:45][CH:44]=1.[OH2:50]>CN(C=O)C.C(OCC)(=O)C>[O:25]=[C:19]1[CH:18]([N:12]2[CH2:11][C:10]3[C:14](=[CH:15][CH:16]=[C:8]([C:7]([NH:6][C:31]([NH:49][C:46]4[CH:47]=[CH:48][C:43]([C:39]5[NH:38][CH:42]=[CH:41][N:40]=5)=[CH:44][CH:45]=4)=[O:32])=[O:50])[CH:9]=3)[CH2:13]2)[CH2:23][CH2:22][C:21](=[O:24])[NH:20]1

Participants

7

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 235069274-(1H-Imidazol-2-yl)anilineHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

Product 1

HCID 66589506HCID 66589506, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonic acid salt (0.40 g, 1.1 mmol) and CDI (0.19 g, 1.2 mmol) in DMF (5 mL) was stirred at room temperature for 18 hours. To the mixture was added 4-(1H-imidazol-2-yl)-phenylamine (0.17 g, 1.1 mmol) at room temperature, and the mixture was stirred at 60° C. for 1d. To the mixture was added water (25 mL) and ethyl acetate (20 mL). The mixture was stirred at room temperature for 2 h. The suspension was filtered and the solid was washed with water (20 mL), ethyl acetate (20 mL) and water (20 mL) to give a solid. The solid was purified with Prep HPLC to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-1-isoindol-5-ylmethyl]-3-[4-(1H-imidazol-2-yl)-phenyl]-urea as a white solid (150 mg. 30% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 5/95 grad 95/5 in 5 min CH1CN/0.1% H3PO4, 4.41 min (95.9%); 190-192° C.; 1H NMR (DMSO-d6) δ 1.91-2.08 (m, 1H, CHH), 2.27-2.47 (m, 1H, CHH), 2.54-2.66 (m, 1H, CHH), 2.81-3.01 (m, 111, CHH), 4.31 (d, J=17.4 Hz, 1H, CHH), 4.38-4.52 (m, 3H, CHH, CH1), 5.11 (dd, J=5.0, 13.3 Hz, 1H, NCH), 6.78 (t, J=6.0 Hz, 1H, NH), 7.33-7.76 (m, 9H, Ar), 8.17 (s, 1H, HCOOH), 8.67 (s, 1H, NH), 10.99 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.41, 31.10, 42.69, 47.02, 51.49, 114.17 (br), 117.80, 121.79, 122.84, 124.55, 126.81, 126.98, 130.19, 135.46, 138.55, 142.31, 144.83, 155.14, 163.19 (HCOOH), 167.88, 170.92, 172.77; LCMS MH=459; Anal. Calcd for C24H22N6O4+2H2O+0.7 HCOOH+0.3 DMF: C, 56.04; H, 5.42; N, 16.08. Found: C, 55.84; H, 5.34; N, 16.11.

Workup

  1. stirringThe mixture was stirred at room temperature for 2 h
  2. filtrationThe suspension was filtered
  3. washthe solid was washed with water (20 mL), ethyl acetate (20 mL) and water (20 mL)
  4. customto give a solid
  5. customThe solid was purified with Prep HPLC

Sources & evidence

ORD record
ord-30dd9d7a407c485c8d4c8f9cd7df3f05
Source dataset
uspto-grants-2012_03
Patent number
US08129375B2

Reaction notes

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