Propyl isocyanate → HCID 16117081, compound

HRID 448282Notes

Reaction equation

HRID 448282 reaction equation
Cl.[NH2:2][CH2:3][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].[CH2:22]([N:25]=[C:26]=[O:27])[CH2:23][CH3:24]>C(#N)C>[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[CH2:3][NH:2][C:26]([NH:25][CH2:22][CH2:23][CH3:24])=[O:27])[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

4

Reactant 2

HCID 61033Propyl isocyanateHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 16117081HCID 16117081, compoundYield 39.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,8-Diazabicyclo[5,4,0]-unded-7-ene (0.8 g, 5.3 mmol) was added to a stirred suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.7 g, 2.1 mmol) in acetonitrile (100 mL). The mixture was stirred for 30 minutes. Propyl isocyanate (0.3 g, 3.2 mmol) was added, and the mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was stirred with CH2Cl2 (60 mL) and 2N HCl (30 mL). The mixture was filtered and the solid was slurried with methanol (40 mL) to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-propyl-urea (0.3 g, 31%) as a white solid: mp 298-300° C.; 1H NMR (DMSO-d6) δ 0.82 (t, J=7.3 Hz, 3H, CH3), 1.32-1.41 (m, 2H), 1.99-2.04 (m, 1H), 2.37-2.65 (m, 2H), 2.86-2.99 (m, 3H), 4.29 (d, J=6.0 Hz, 2H), 4.37 (d, J=17.3 Hz, 1H), 4.45 (d, J=17.3 Hz, 1H), 5.11-5.18 (dd, J=5.1 and 13.2 Hz, 1H, CH), 6.00 (t, J=5.5 Hz, 1H, NH), 6.38 (t, J=5.9 Hz, 1H, NH), 7.47-7.62 (m, 3H, Ar), 11.03 (s, 1H, NH); 13C NMR (DMSO-d6) δ 11.31, 22.62, 23.24, 31.18, 41.16, 46.13, 51.50, 121.36, 128.19, 130.24, 131.58, 136.29, 139.80, 157.97, 168.13, 171.01, 172.87; Anal. calcd. for C18H22N4O4: C, 60.32; H, 6.19; N, 15.63. Found: C, 59.93; H, 6.27; N, 15.40.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. concentrationThe mixture was concentrated
  3. stirringthe residue was stirred with CH2Cl2 (60 mL) and 2N HCl (30 mL)
  4. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-3af6f24fea4e435daf10d814c2beb001
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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