Dichloromethane → HCID 58827270, compound

HRID 448459Notes

Reaction equation

HRID 448459 reaction equation
[ClH:1].[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[C:33]1[CH:34]=[C:35]([CH:39]=C(F)[CH:41]=1)[C:36](Cl)=[O:37].[CH2:43]([Cl:45])Cl>>[Cl:1][C:33]1[CH:34]=[C:35]([CH:39]=[C:43]([Cl:45])[CH:41]=1)[C:36]([NH: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])=[O:37]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 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 58827270HCID 58827270, compoundYield 76%

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 (0.59 g, 2.8 mmol). This 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 stirred with acetone (10 mL). The resulting suspension was filtered, and the solid was washed with acetone and dried in vacuum oven to afford 3,5-dichloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamide as a white solid (0.8 g, 76%): mp, 250-252° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 50/50 (CH3CN/H2O): tR=4.3 min (96%); 1H NMR (DMSO-d6): δ 2.05-2.11 (m, 1H), 2.53-2.64 (m, 2H), 2.85-2.93 (m, 1H), 4.95 (d, J=5.7 Hz, 2H), 5.15-5.21 (dd, J=5, 12 Hz, 1H), 7.76-7.94 (m, 6H), 9.37 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.97, 30.92, 38.54, 48.86, 121.99, 126.20, 127.21, 130.82, 131.52, 133.27, 134.32, 134.83, 137.11, 138.54, 163.94, 166.92, 167.47, 169.81, 172.74. Anal Calcd for C21H15Cl2N3O5: C, 54.80; H, 3.28; N, 9.13; Cl, 15.41. Found: C, 54.93; H, 2.96; N, 9.01; Cl, 15.62.

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. stirringthe resulting mixture was stirred with acetone (10 mL)
  7. filtrationThe resulting suspension was filtered
  8. washthe solid was washed with acetone
  9. customdried in vacuum oven

Sources & evidence

ORD record
ord-054106fe939f48688e0af7d33e4f1bfa
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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