Methanol → HCID 58827337, compound

HRID 448468Notes

Reaction equation

HRID 448468 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.[CH3:32][O:33][C:34]1[CH:35]=[C:36]([CH:40]=[CH:41][C:42]=1[O:43][CH3:44])[C:37](Cl)=[O:38].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:42]([O:43][CH3:44])=[C:34]([O:33][CH3:32])[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 77070Veratroyl chlorideHCID 81531DiisopropylethylamineHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827337HCID 58827337, compoundYield 82%

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 3,4-dimethyoxybenzoyl chloride (0.6 g, 2.8 mmol). The mixture was stirred at room temperature overnight followed by the addition of MeOH (1 mL). The reaction mixture was then washed with water (40 mL), 1N HCl (2×40 mL), and brine (40 mL), dried over MgSO4, and concentrated in vacuo. The resulting oil was purified by ISCO silica gel flash chromatography (eluent: 0% MeOH in CH2Cl2 to 5% MeOH in 10 min then stay at this ratio for 15 min) to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl-methyl]-3,4-dimethoxy-benzamide as a white solid (0.8 g, 79%): mp, 198-200° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=2.2 min. (99%); 1H NMR (DMSO-d6): δ 2.06-2.10 (m, 1H), 2.51-2.59 (m, 2H), 2.64 (m, 1H), 3.81 (s, 6H), 4.94 (d, J=5.9 Hz, 2H), 5.14-5.20 (dd, J=5, 12 Hz, 1H), 7.06 (d, J=8.5 Hz, 1H), 7.51-7.58 (m, 2H), 7.83-7.70 (m, 3H), 9.02 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.97, 30.92, 38.22, 48.86, 55.53, 55.60, 110.67, 110.92, 120.56, 121.80, 126.10, 127.05, 131.50, 133.06, 134.77, 139.66, 148.28, 151.44, 166.09, 166.96, 167.57, 169.83, 172.74. Anal Calcd for C23H21N3O7+0.2H2O: C, 60.71; H, 4.74; N, 9.23. Found: C, 60.39; H, 4.51; N, 8.99.

Workup

  1. washThe reaction mixture was then washed with water (40 mL), 1N HCl (2×40 mL), and brine (40 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe resulting oil was purified by ISCO silica gel flash chromatography (eluent
  5. wait0% MeOH in CH2Cl2 to 5% MeOH in 10 min then stay at this ratio for 15 min

Sources & evidence

ORD record
ord-ab6d548aa7da49e1ac0d1130f2a5538f
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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