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1,8-Diazabicyclo(5.4.0)undec-7-ene → 1,5-dimethyl-1H-pyrazole-3-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide

HRID 448451
Notes
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Reaction equation

HRID 448451 reaction equation
N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17](=[O:33])[N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].[CH3:34][N:35]1[C:39]([CH3:40])=[CH:38][C:37]([C:41](Cl)=[O:42])=[N:36]1>C(#N)C>[O:32]=[C:26]1[CH:25]([N:18]2[C:17](=[O:33])[C:16]3[C:20](=[CH:21][CH:22]=[CH:23][C:15]=3[CH2:14][NH:13][C:41]([C:37]3[CH:38]=[C:39]([CH3:40])[N:35]([CH3:34])[N:36]=3)=[O:42])[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27763641,5-Dimethyl-1H-Pyrazole-3-Carbonyl ChlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 588273221,5-dimethyl-1H-pyrazole-3-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amideYield 38%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,8-Diazabicyclo[5.4.0]undec-7-ene (1.0 g, 6.6 mmol) was added to a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.0 mmol) in acetonitrile (40 mL). After stirring for 10 minutes, 1,5-dimethyl-1H-pyrazole-3-carbonyl chloride (0.4 g, 2.6 mmol) was added. The mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was dissolved in CH2Cl2 (80 mL). The CH2Cl2 solution was washed with water (2×30 mL) and brine (30 mL), and dried (MgSO4). Solvent was removed, and the residue was purified by chromatography (SiO2, CH2Cl2: CH3OH 97.5:2.5) to give 1,5-dimethyl-1H-pyrazole-3-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide (0.3 g, 38%) as a white solid: mp 213-215° C.; 1H NMR (DMSO-d6) δ 2.05-2.09 (m, 1H), 2.28 (s, 3H), 2.50-2.64 (m, 2H), 2.84-2.97 (m, 1H), 3.79 (s, 3H), 4.86 (d, J=5.9 Hz, 2H), 5.13-5.20 (dd, J=5.1 and 12.4 Hz, 1H), 6.44 (s, 1H), 7.65-7.79 (m, 3H), 8.69 (t. J=5.9 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 10.66, 21.97, 30.93, 36.39, 37.80, 48.86, 105.53, 121.71, 127.01, 131.51, 132.78, 134.70, 139.60, 140.35, 144.26, 161.91, 167.00, 167.56, 169.83, 172.75; Anal. calcd. for C20H19N5O5+0.4H2O: C, 57.66; H, 4.79; N, 16.81. Found: C, 57.85; H, 4.80; N, 16.64.

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationThe mixture was concentrated
  3. dissolutionthe residue was dissolved in CH2Cl2 (80 mL)
  4. washThe CH2Cl2 solution was washed with water (2×30 mL) and brine (30 mL)
  5. dry with materialdried (MgSO4)
  6. customSolvent was removed
  7. customthe residue was purified by chromatography (SiO2, CH2Cl2: CH3OH 97.5:2.5)

Sources & evidence

ORD record
ord-a002226b0c044acc9fdf5735e1af88df
Source dataset
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08481568B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes