3,4-Dimethylphenyl isocyanate → HCID 24895902, compound

HRID 240680Notes

Reaction equation

HRID 240680 reaction equation
Cl.[O:2]=[C:3]1[CH:8]([N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[CH2:19][NH:20][CH3:21])[C:10]2=[O:22])[CH2:7][CH2:6][C:5](=[O:23])[NH:4]1.[CH3:24][C:25]1[CH:26]=[C:27]([N:32]=[C:33]=[O:34])[CH:28]=[CH:29][C:30]=1[CH3:31]>C(Cl)Cl>[CH3:24][C:25]1[CH:26]=[C:27]([NH:32][C:33](=[O:34])[N:20]([CH2:19][C:15]2[CH:14]=[CH:13][CH:12]=[C:11]3[C:16]=2[C:17](=[O:18])[N:9]([CH:8]2[CH2:7][CH2:6][C:5](=[O:23])[NH:4][C:3]2=[O:2])[C:10]3=[O:22])[CH3:21])[CH:28]=[CH:29][C:30]=1[CH3:31]

Participants

4

Reactant 2

HCID 43896633,4-Dimethylphenyl isocyanateHCID 67026649HCID 67026649, compound

Product 1

HCID 24895902HCID 24895902, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-(2,6-dioxo-piperidin-3-yl)-4-methylaminomethyl-isoindole-1,3-dione hydrochloride (0.65 g, 1.93 mmol) and 3,4-dimethylphenyl isocyanate (0.32 mL, 2.31 mmol) in dry CH2Cl2 (80 ml), was added diidopropylethylamine (0.47 mL g, 2.60 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was quenched with MeOH (1 mL). The suspension was filtered, and the resulting solid cake was rinsed with CH2Cl2 (5 ml). The solid was reslurried with ether (I 5 mL) to give 3-(3,4-dimethyl-phenyl)-1-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-1-methyl-urea as a solid (0.51 g, 59%)): mp 202-204° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=6.23 (99%); 1H NMR (DMSO-d6): δ 2.14 (s, 3H), 2.16 (s, 3H), 2.54-2.64 (m, 2H), 2.85-2.97 (m, 1H), 3.03 (s, 3H), 5.00 (s, 2H), 5.14-5.20 (dd, J=5.3, 12.6 Hz, 1H), 6.99 (d, J=8.2 Hz, 1H), 7.19 (d, J=8.1 Hz, 1H), 7.26 (s, 1H), 7.61 (d, J=7.2 Hz, 1H), 7.89-7.81 (m, 2H), 8.34 (s, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 18.62, 15.54, 21.97, 30.91, 35.10, 47.46, 48.85, 117.61, 121.43, 121.83, 127.54, 129.12, 129.51, 131.78, 132.42, 134.95, 135.63, 137.93, 138.97, 155.79, 16696, 167.58, 169.80, 172.74. Anal Calcd for C24H24N4O5: C, 64.28; H, 5.39; N, 12.49. Found: C, 63.99; H, 5.26; N, 12.39.

Workup

  1. additionwas added diidopropylethylamine (0.47 mL g, 2.60 mmol)
  2. customThe reaction mixture was quenched with MeOH (1 mL)
  3. filtrationThe suspension was filtered
  4. washthe resulting solid cake was rinsed with CH2Cl2 (5 ml)

Sources & evidence

ORD record
ord-7e2196f38e924776b8630647424bf99d
Source dataset
uspto-grants-2014_02
Patent number
US08648096B2

Reaction notes

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