Methanol → HCID 58827332, compound

HRID 448472Notes

Reaction equation

HRID 448472 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:41]=[CH:40][C:36]([C:37](Cl)=[O:38])=[CH:35][CH:34]=1.CO>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:37](=[O:38])[C:36]3[CH:40]=[CH:41][C:33]([F:32])=[CH:34][CH:35]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

6

Reactant 4

HCID 887MethanolHCID 678794-Fluorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827332HCID 58827332, compoundYield 59%

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 4-fluorobenzoyl chloride (0.45 g, 2.8 mmol). The mixture was stirred at room temperature overnight followed by addition of MeOH (1 mL). After filtration, the resulting solid was washed with CH2Cl2 then recrystallized in CH3OH to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-benzamide as a white solid (0.5 g, 59%): mp, 233-235° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=3.6 (96%); 1H NMR (DMSO-d6): δ 2.06-2.11 (m, 1H), 2.53-2.64 (m, 2H), 2.86-2.98 (m, 1H), 4.95 (d, J=5.7 Hz, 2H), 5.15-5.21 (dd, J=5, 12 Hz, 1H), 7.30-7.38 (m, 2H), 7.72-7.86 (m, 3H), 7.96-8.03 (m2H), 9.18 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.97, 30.92, 38.35, 48.86, 115.15, 115.44, 121.87, 127.12, 129.91, 130.03, 130.37, 131.52, 133.05, 134.80, 139.21, 162.35, 165.54, 165.64, 166.95, 167.52, 169.82, 172.74. Anal Calcd for C21H16FN3O5: C, 66.61; H, 3.94; N, 10.26; F, 4.64. Found: C, 61.53; H, 3.82; N, 10.20; F, 4.72.

Workup

  1. filtrationAfter filtration
  2. washthe resulting solid was washed with CH2Cl2
  3. customthen recrystallized in CH3OH

Sources & evidence

ORD record
ord-4286661a1889498ebeb28c6511e2dd3b
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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