3-Chloro-4-methylphenyl isocyanate → HCID 58827316, compound

HRID 448423Notes

Reaction equation

HRID 448423 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].[Cl:23][C:24]1[CH:25]=[C:26]([N:31]=[C:32]=[O:33])[CH:27]=[CH:28][C:29]=1[CH3:30].C(N(C(C)C)CC)(C)C>N1C=CC=CC=1>[Cl:23][C:24]1[CH:25]=[C:26]([NH:31][C:32]([NH:2][CH2:3][C:4]2[CH:12]=[CH:11][CH:10]=[C:9]3[C:5]=2[C:6](=[O:22])[N:7]([CH:14]2[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]2=[O:21])[C:8]3=[O:13])=[O:33])[CH:27]=[CH:28][C:29]=1[CH3:30]

Participants

5

Reactant 3

HCID 628323-Chloro-4-methylphenyl isocyanateHCID 81531DiisopropylethylamineHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827316HCID 58827316, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.50 g, 1.6 mmol), 3-chloro-4-methylphenyl isocyanate (0.26 g, 1.6 mmol), and diisopropylethylamine (0.40 g, 3.1 mmol) in 10 mL pyridine was warmed to 40° C. with stirring under N2, and the resulting solution was stirred at the same temperature for 2 hours. The mixture was cooled, and the solvent was evaporated under vacuum. The residue was chromatographed, eluting with 95:5 methylene chloride-methanol, to provide 0.63 g of the product in 90% yield: mp 238-240° C.; 1H NMR (DMSO-d6) δ 2.05-2.10 (m, 1H), 2.22 (s, 3H), 2.49-2.65 (m, 2H), 2.84-2.97 (m, 1H), 4.70 (d, J=6.0 Hz, 2H), 5.17 (dd, J=12.5 Hz, d=5.3 Hz, 1H), 6.81 (t, J=6.0 Hz, 1H), 7.10 (dd, J=8.3 Hz, J=2.0 Hz, 1H), 7.18 (d, J=8.3 Hz, 1H), 7.65 (d, J=2.0 Hz, 1H), 7.75-7.85 (m, 3H), 8.90 (s, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 18.7, 22.0, 30.9, 38.7, 48.9, 116.4, 117.6, 121.9, 127.2, 127.5, 131.0, 131.6, 133.0, 133.7, 134.7, 139.5, 140.1, 155.1, 167.0, 167.6, 169.8, 172.8; Anal. calcd. for C22H19ClN4O5.0.25H2O: C, 57.52; H, 4.27; N, 12.19. Found: C, 57.80; H, 4.33; N, 11.83.

Workup

  1. stirringthe resulting solution was stirred at the same temperature for 2 hours
  2. temperatureThe mixture was cooled
  3. customthe solvent was evaporated under vacuum
  4. customThe residue was chromatographed
  5. washeluting with 95:5 methylene chloride-methanol

Sources & evidence

ORD record
ord-7f82a954c85246c181e5211af05f4378
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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