Diisopropylethylamine → HCID 58827331, compound

HRID 448456Notes

Reaction equation

HRID 448456 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]=[CH:40][C:41]=1[F:42])[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:39]=[CH:40][C:41]([F:42])=[C:33]([F:32])[CH:34]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27245193,4-Difluorobenzoyl chlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827331HCID 58827331, compoundYield 75.8%

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-difluorobenzoyl chloride (0.5 g, 2.8 mmol). The mixture was stirred at room temperature overnight and a suspension was obtained. The reaction mixture was quenched with MeOH (1 mL) and was filtered. The solid was rinsed with CH2Cl2 (5 mL) and then dissolved in acetone (4 mL). Ether (10 mL) and hexane (10 mL) were added to the solution and the resulting suspension was filtered to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3,4-difluoro-benzamide as a white solid (0.7 g, 75%): 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=4.1 min. (99%); 1H NMR (DMSO-d6): δ 2.06-2.11 (m, 1H), 2.51-2.64 (m, 2H), 2.87-2.93 (m, 1H), 4.95 (d, J=5.8 Hz, 2H), 5.15-5.21 (dd, J=5, 12 Hz, 1H), 7.55-8.01 (m, 6H), 9.26 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.96, 30.92, 39.20, 48.86, 116.77, 116.65, 116.89, 117.51, 117.74, 121.95, 124.75, 124.80, 124.85, 124.89, 127.18, 131.28, 131.32, 131.39, 131.53, 133.15, 134.82, 138.86, 147.42, 147.59, 149.70, 149.87, 150.68, 150.85, 153.02, 153.19, 164.45, 166.93, 167.49, 169.81, 172.74. Anal Calcd for C21H15F2N3O5: C, 59.02; H, 3.54; N, 9.83; F, 8.89. Found: C, 59.12; H, 3.60; N, 9.68; F, 8.86.

Workup

  1. customa suspension was obtained
  2. customThe reaction mixture was quenched with MeOH (1 mL)
  3. filtrationwas filtered
  4. washThe solid was rinsed with CH2Cl2 (5 mL)
  5. dissolutiondissolved in acetone (4 mL)
  6. additionEther (10 mL) and hexane (10 mL) were added to the solution
  7. filtrationthe resulting suspension was filtered

Sources & evidence

ORD record
ord-33afec2293e0417e8bce0fb484c990a8
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

Loading…