Diisopropylethylamine → N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-3-trifluoromethyl-benzamide

HRID 448497Notes

Reaction equation

HRID 448497 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].[F:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][C:25]=1[C:33]([F:36])([F:35])[F:34].C(N(C(C)C)CC)(C)C>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:28](=[O:29])[C:27]3[CH:31]=[CH:32][C:24]([F:23])=[C:25]([C:33]([F:36])([F:34])[F:35])[CH:26]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1442534-Fluoro-3-(trifluoromethyl)benzoyl ChlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 67229011N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-3-trifluoromethyl-benzamideYield 79%

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, 2.2 mmol) and 4-fluoro-3-trifluoromethyl-benzoyl chloride (0.6 g, 2.8 mmol) in dry methylene chloride (60 mL), was added diisopropylethylamine (0.7 g, 5.4 mmol). After stirring at room temperature overnight, the reaction mixture was quenched with methanol (1 mL). The resulting suspension was filtered, and the solid was washed with methyene chloride to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-3-trifluoromethyl-benzamide (0.8 g, 79%) as a white solid: mp 171-173° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=7.5 min. (99%); 1H NMR (DMSO-d6) δ 2.06-2.12 (m, 1H), 2.54-2.65 (m, 2H), 2.85-2.98 (m, 1H), 4.97 (d, J=5.7 Hz, 2H), 5.15-5.21 (dd, J=5.4 and 12.5 Hz, 1H), 7.68 (t, J=8.9 Hz, 1H), 7.76-7.84 (m, 3H), 8.28-8.35 (m, 2H), 9.43 (t, J=5.7 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 21.91, 30.86, 38.43, 48.82, 116.20 (116.37, 116.64, 116.80), 117.35 (117.63), 120.50 (124.10), 121.92, 126.51 (126.56), 127.14, 130.65 (130.70), 131.48, 133.22, 134.58, 134.71 (134.77), 138.70, 158.78 (162.21), 164.19, 166.87, 167.44, 169.75, 172.68; Anal. Calcd. for C22H15N3O5F4+0.2H2O: C, 54.94; H, 3.23; N, 8.74; F, 15.80. Found: C, 54.68; H, 3.17; N, 8.63; F, 15.72.

Workup

  1. customthe reaction mixture was quenched with methanol (1 mL)
  2. filtrationThe resulting suspension was filtered
  3. washthe solid was washed with methyene chloride

Sources & evidence

ORD record
ord-0a96e7434fec48308601c3accc2a41e0
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

Loading…