1-Hydroxybenzotriazole → HCID 58827239, compound

HRID 448479Notes

Reaction equation

HRID 448479 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:57])([F:56])[C:46]1[CH:51]=[CH:50][C:49]([CH2:52][C:53](O)=[O:54])=[CH:48][CH:47]=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:53](=[O:54])[CH2:52][C:49]3[CH:48]=[CH:47][C:46]([C:45]([F:56])([F:44])[F:57])=[CH:51][CH:50]=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 118342(alpha,alpha,alpha-Trifluoro-4-tolyl)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827239HCID 58827239, compoundYield 71%

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-(trifluoromethyl)phenylacetic acid (0.6 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) then 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-trifluoromethyl-phenyl)-acetamide (0.7 g, 71%) as a white solid: mp 144-146° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=5.58 min. (97%); 1H NMR (DMSO-d6) δ 2.03-2.08 (m, 1H), 2.51-2.63 (m, 2H), 2.84-2.91 (m, 1H), 3.66 (s, 2H), 4.74 (d, J=5.9 Hz, 2H), 5.12-5.18 (dd, J=5.3 and 12.7 Hz, 1H), 7.50-7.82 (m, 7H), 8.75 (t, J=5.8 Hz, 1H), 11.14 (s, 1H); 13C NMR (DMSO-d6) δ 21.94, 30.90, 37.89, 41.75, 48.83, 121.93, 124.95 (125.01, 125.05, 125.10), 122.56 (126.16), 126.96 (127.15, 127.38), 129.94, 131.52, 133.26, 134.69, 138.95, 140.95, 166.88, 167.41, 169.78, 169.87, 172.73; Anal. Calcd. for C23H18N3O5F3: C, 58.35; H, 3.83; N, 8.88; F, 12.04. Found: C, 58.19; H, 3.53; N, 8.73; F, 12.07.

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. washthen 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-1fb70c5c85cd4df8af74c500d24703fb
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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