alpha-Naphthyl isocyanate → HCID 24895998, compound

HRID 240681Notes

Reaction equation

HRID 240681 reaction equation
Cl.CN[C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][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:22]1([N:32]=[C:33]=[O:34])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][CH:23]=1.[CH:35]([N:38](C(C)C)[CH2:39]C)(C)C>C(Cl)Cl>[O:21]=[C:15]1[CH:14]([N:7]2[CH2:6][C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:35][N:38]([CH3:39])[C:33]([NH:32][C:22]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=[CH:24][CH:23]=3)=[O:34])[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

5

Reactant 3

HCID 66589alpha-Naphthyl isocyanateHCID 81531DiisopropylethylamineHCID 67026753HCID 67026753, compound

Product 1

HCID 24895998HCID 24895998, compoundYield 89.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-(4-methylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.60 g, 1.86 mmol) and 1-naphthyl isocyanate (0.32 mL, 2.23 mmol) in dry CH2Cl2 (80 ml), was added diisopropylethylamine (0.45 mL g, 2.60 mmol). The mixture was stirred at room temperature overnight. The mixture was quenched with MeOH and filtered. The resulting solid was rinsed with CH2Cl2 (5 mL) to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-1-methyl-3-naphthalen-1-yl-urea (0.76 g, 89%): mp 292-294° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=2.65 (99%); 1H NMR (DMSO-d6): δ 2.00-2.05 (m, 1H), 2.29-2.35 (m, 1H), 2.56-2.62 (m, 1H), 2.87-2.97 (m, 1H), 3.09 (s, 3H), 4.40 (d, J=17.3 Hz, 1H), 4.47 (d, J=17.4 Hz, 1H), 4.72 (s, 2H), 5.13-5.19 (dd, J=5.1, 13.3 Hz, 1H), 7.47-7.93 (m, 10H), 8.57 (s, 1H), 11.04 (s, 1H). 13C NMR (DMSO-d6) δ: 22.62, 31.14, 34.78, 46.20, 48.55, 51.52, 121.70, 123.30, 123.38, 125.46, 125.48, 125.74, 127.87, 128.42, 129.63, 129.91, 131.95, 133.71, 133.99, 135.39, 140.17, 156.71, 168.02, 170.99, 172.81. Anal Calcd for C26H24N4O4: C, 68.41; H, 5.30; N, 12.27. Found: C, 68.54; H, 5.12; N, 11.87.

Workup

  1. customThe mixture was quenched with MeOH
  2. filtrationfiltered
  3. washThe resulting solid was rinsed with CH2Cl2 (5 mL)

Sources & evidence

ORD record
ord-3c61290d482c427fb21ef0a1e3596efc
Source dataset
uspto-grants-2014_02
Patent number
US08648096B2

Reaction notes

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