Dimethylcarbamoyl Chloride → HCID 53246790, compound

HRID 448295Notes

Reaction equation

HRID 448295 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH2:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[CH2:13][N:14]([CH:21]1[CH2:26][CH2:25][C:24](=[O:27])[NH:23][C:22]1=[O:28])[C:15]2=[O:20].[CH3:29][N:30]([CH3:34])[C:31](Cl)=[O:32].N12CCCN=C1CCCCC2>C1COCC1>[O:28]=[C:22]1[CH:21]([N:14]2[CH2:13][C:12]3[C:16](=[CH:17][CH:18]=[CH:19][C:11]=3[CH2:10][NH:9][C:31](=[O:32])[N:30]([CH3:34])[CH3:29])[C:15]2=[O:20])[CH2:26][CH2:25][C:24](=[O:27])[NH:23]1

Participants

6

Reactant 4

HCID 6598Dimethylcarbamoyl Chloride2×HCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 53246790HCID 53246790, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (0.6 g, 5.9 mmol) was added slowly 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) and dimethylcarbamoyl chloride (0.3 g, 3.2 mmol) in THF (100 mL). The mixture was stirred at room temperature overnight. Another portion of dimethylcarbamoyl chloride (0.3 g) and 1,8-diazabicyclo[5,4,0]-undec-7-ene (0.6 g) was added and stirred for another day. The mixture was concentrated, and the residue was stirred with 1N HCl (15 mL). The mixture was filtered, and the solid was slurried with hot methanol (10 mL) to give 3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-1,1-dimethyl-urea (0.3 g, 46%) as a white solid: mp 169-171° C.; 1H NMR (DMSO-d6) δ 1.99-2.04 (m, 1H), 2.32-2.64 (m, 2H), 2.80 (s, 6H, 2CH3), 2.85-3.00 (m, 1H), 4.27 (d, J=5.6 Hz, 2H, CH2), 4.40 (d, J=17.3 Hz, 1H), 4.47 (d, J=17.3 Hz, 1H), 5.10-5.17 (dd, J=5.0 and 13.2 Hz, 1H, CH), 6.94 (t, J=5.6 Hz, 1H, NH), 7.44-7.64 (m, 3H, Ar), 11.02 (s, 1H); 13C NMR (DMSO-d6) δ 22.58, 31.18, 35.88, 46.20, 51.55, 121.20, 128.08, 130.38, 131.39, 136.35, 139.77, 158.08, 168.15, 171.00, 172.83; Anal. calcd. for C17H20N4O4: C, 59.29; H, 5.85; N, 16.27. Found: C, 59.05; H, 5.91; N, 15.92.

Workup

  1. stirringstirred for another day
  2. concentrationThe mixture was concentrated
  3. stirringthe residue was stirred with 1N HCl (15 mL)
  4. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-20fa3124ff1c4b6ea962d36e200e3c6c
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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