1-Hydroxybenzotriazole → HCID 58827280, compound

HRID 448477Notes

Reaction equation

HRID 448477 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].N12CCCN=C1CCCCC2.ON1C2C=CC=CC=2N=N1.[F:44][C:45]([F:58])([F:57])[O:46][C:47]1[CH:52]=[CH:51][C:50]([CH2:53][C:54](O)=[O:55])=[CH:49][CH:48]=1.Cl.CN(C)CCCN=C=NCC>C(#N)C>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:54](=[O:55])[CH2:53][C:50]3[CH:51]=[CH:52][C:47]([O:46][C:45]([F:57])([F:44])[F:58])=[CH:48][CH:49]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27773192-[4-(Trifluoromethoxy)phenyl]acetic acidHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827280HCID 58827280, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) in acetonitrile (60 mL), was added 1,8-diazabicyclo[5,4,0]undec-7-ene (0.8 g, 5.4 mmol). After stirring for 10 minutes, 1-hydroxybenzotriazole (0.4 g, 2.6 mmol) and 4-trifluoromethoxyphenylacetic acid (0.5 g, 2.4 mmol) were added, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.6 g, 3.2 mmol). After stirring at room temperature overnight, the reaction mixture was concentrated in vacuo. The residue was dissolved in CH2Cl2 (80 mL), and the solution was washed with water (40 mL), 1NHCl (2×30 mL), water (40 mL), and brine (40 mL), and dried over MgSO4. Solvent was removed in vacuo, and the residue was purified by ISCO silica gel flash chromatography (Eluent: EtOAc: CH2Cl2=4:6) to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-(4-trifluoromethoxy-phenyl)-acetamide (0.7 g, 64%) as a white solid: mp 134-136° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=6.41 min. (98%); 1H NMR (DMSO-d6) δ 2.03-2.08 (m, 1H), 2.52-2.63 (m, 2H), 2.84-2.91 (m, 1H), 3.59 (s, 2H), 4.73 (d, J=5.8 Hz, 2H), 5.12-5.18 (dd, J=5.3 and 12.7 Hz, 1H), 7.29-7.32 (d, J=8.6 Hz, 2H), 7.40-7.43 (d, J=8.7 Hz, 2H), 7.63-7.82 (m, 2H), 8.72 (t, J=5.9 Hz, 1H), 11.14 (s, 1H); 13C NMR (DMSO-d6) δ 21.94, 30.90, 37.85, 41.23, 48.83, 120.81, 118.37 (121.76, 125.15), 121.91, 127.14, 130.91, 131.52, 133.22, 134.65, 135.64, 139.02, 147.02, 166.88, 167.41, 169.78, 170.21, 172.72; Anal. Calcd. for C23H18N3O6F3: C, 56.45; H, 3.71; N, 8.59; F, 11.65. Found: C, 56.20; H, 3.39; N, 8.44; F, 11.87.

Workup

  1. stirringAfter stirring at room temperature overnight
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in CH2Cl2 (80 mL)
  4. washthe solution was washed with water (40 mL), 1NHCl (2×30 mL), water (40 mL), and brine (40 mL)
  5. dry with materialdried over MgSO4
  6. customSolvent was removed in vacuo
  7. customthe residue was purified by ISCO silica gel flash chromatography (Eluent: EtOAc: CH2Cl2=4:6)

Sources & evidence

ORD record
ord-e0b25ef1ab144e4db391a151fb74ecb7
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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