1-Hydroxybenzotriazole → HCID 58307310, compound

HRID 448491Notes

Reaction equation

HRID 448491 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.[CH3:44][C:45]1[S:46][C:47]([CH3:54])=[C:48]([CH2:50][C:51](O)=[O:52])[N:49]=1.Cl.CN(C)CCCN=C=NCC>C(#N)C>[CH3:44][C:45]1[S:46][C:47]([CH3:54])=[C:48]([CH2:50][C:51]([NH:2][CH2:3][C:4]2[CH:12]=[CH:11][CH:10]=[C:9]3[C:5]=2[C:6](=[O:22])[N:7]([CH:14]2[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]2=[O:21])[C:8]3=[O:13])=[O:52])[N:49]=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 27475832,5-Dimethyl-4-thiazoleacetic acidHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58307310HCID 58307310, compoundYield 76%

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 2-(2,5-dimethyl-1,3-thiazol-4-yl)acetic acid (0.4 g, 2.4 mmol) were added, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.6 g, 3.2 mmol). The mixture was stirred at room temperature overnight and concentrated in vacuo. The residue was dissolved in CH2Cl2 (80 mL) and washed with water (3×40 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: CH3OH: CH2Cl2 3:97) to afford 2-(2,5-dimethyl-1,3-thiazol-4-yl)-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide (0.7 g, 76%) as a white solid: mp 140-142° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=1.39 min. (99%); 1H NMR (DMSO-d6) δ 2.04-2.09 (m, 1H), 2.31 (s, 3H), 2.56 (s, 3H), 2.51-2.63 (m, 2H), 2.84-2.91 (m, 1H), 3.56 (s, 2H), 4.73 (d, J=5.9 Hz, 2H), 5.12-5.18 (dd, J=5.3 and 12.7 Hz, 1H), 7.76-7.85 (m, 3H), 8.58 (t, J=6.0 Hz, 1H), 11.13 (s, 1H); 13C NMR (DMSO-d6) δ 10.84, 18.56, 21.95, 30.91, 35.85, 37.94, 48.82, 121.81, 127.03, 127.91, 131.46, 133.21, 134.60, 139.26, 145.51, 160.87, 166.94, 167.48, 169.51, 169.79, 172.73; Anal. Calcd. for C21H20N4O5S: C, 57.27; H, 4.58; N, 12.72; S, 7.28. Found: C, 57.13; H, 4.71; N, 12.45; S, 7.18.

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in CH2Cl2 (80 mL)
  4. washwashed with water (3×40 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: CH3OH: CH2Cl2 3:97)

Sources & evidence

ORD record
ord-1f040ad678104cb9a2dd76f15eafe9b5
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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