Diisopropylethylamine → HCID 58827335, compound

HRID 448469Notes

Reaction equation

HRID 448469 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]([F:45])([F:44])[O:34][C:35]1[CH:43]=[CH:42][C:38]([C:39](Cl)=[O:40])=[CH:37][CH:36]=1>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:39](=[O:40])[C:38]3[CH:42]=[CH:43][C:35]([O:34][C:33]([F:32])([F:44])[F:45])=[CH:36][CH:37]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1421104-(Trifluoromethoxy)benzoyl ChlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827335HCID 58827335, compoundYield 78%

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-trifluoromethoxybenzoyl chloride (0.6 g, 2.8 mmol). The mixture was then stirred at room temperature overnight. The reaction mixture was quenched with MeOH (1 mL), 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-ylmethyl]-4-trifluoromethoxy-benzamide as an off-white solid (0.8 g, 78%): mp, 163-165° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=7.3 min. (99%); 1H NMR (DMSO-d6): δ 2.07-2.10 (m, 1H), 2.51-2.64 (m, 2H), 2.91-2.92 (m, 1H), 4.96 (d, J=5.7 Hz, 2H), 5.15-5.21 (dd, J=5, 12 Hz, 1H), 7.52 (d, J=8.0 Hz, 2H), 7.74-7.84 (m, 3H), 8.04-8.07 (dd, J=6.8, 1.9 Hz, 2H), 9.28 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.97, 30.92, 38.44, 118.23, 120.68, 121.64, 121.90, 127.15, 129.30, 129.67, 131.53, 133.01, 133.07, 134.80, 139.03, 150.39, 150.42, 165.39, 166.94, 167.51, 169.81, 172.74. Anal Calcd for C22H16F3N3O6: C, 55.59; H, 3.39; N, 8.84; F, 11.99. Found: C, 55.43; H, 3.00; N, 8.76; F, 11.77.

Workup

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

Sources & evidence

ORD record
ord-a547c33b01e347599eb2b423be4c688b
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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