Diisopropylethylamine → HCID 58827307, compound

HRID 448460Notes

Reaction equation

HRID 448460 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].C(N(C(C)C)CC)(C)C.[F:32][C:33]1[CH:34]=[C:35]([CH:39]=[C:40]([F:42])[CH:41]=1)[C:36](Cl)=[O:37]>C(Cl)Cl>[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:36](=[O:37])[C:35]3[CH:34]=[C:33]([F:32])[CH:41]=[C:40]([F:42])[CH:39]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1456003,5-Difluorobenzoyl chlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827307HCID 58827307, compoundYield 54.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.16 mmol) in CH2Cl2 (60 ml) was added diisopropylethylamine (0.94 mL, 5.4 mmol) and 3,5-difluorobenzoyl chloride (0.5 g, 2.8 mmol). The reaction mixture was stirred at room temperature overnight and a suspension was obtained. The reaction mixture was then quenched with MeOH (1 mL) and washed with H2O (40 mL), 1N HCl (40 mL) and brine (40 mL). The organic layer was dried over MgSO4 and concentrated in vacuo, and the resulting mixture was purified by ISCO silica gel flash chromatography (eluent: 3% MeOH in CH2Cl2 for 10 min, then 5% MeOH in CH2Cl2 for 10 min) to afford N-[2-(2,6-Dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3,5-difluoro-benzamide as a white solid (0.5 g, 54%): mp, 218-220° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=4.4 min. (99%); 1H NMR (DMSO-d6): δ 2.06-2.11 (m, 1H), 2.53-2.65 (m, 2H), 2.85-2.93 (m, 1H), 4.96 (d, J=5.8 Hz, 2H), 5.15-5.21 (dd, J=5, 12 Hz, 1H), 7.46-7.84 (m, 6H), 9.33 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.96, 30.92, 38.49, 48.86, 106.93, 110.58, 110.69, 110.82, 110.93, 121.99, 127.21, 131.54, 133.20, 134.83, 137.42, 138.62, 160.51, 160.67, 163.78, 163.95, 164.10, 166.92, 167.48, 169.81, 172.73. Anal Calcd for C21H15F2N3O5: C, 59.02; H, 3.54; N, 9.83. Found: C, 58.90; H, 3.15; N, 9.73.

Workup

  1. customa suspension was obtained
  2. customThe reaction mixture was then quenched with MeOH (1 mL)
  3. washwashed with H2O (40 mL), 1N HCl (40 mL) and brine (40 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customthe resulting mixture was purified by ISCO silica gel flash chromatography (eluent
  7. wait3% MeOH in CH2Cl2 for 10 min

Sources & evidence

ORD record
ord-01a301683e0446fa8b1ebb8acd1b65e5
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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