Dimethylamine tetrahydrofuran → HCID 67228906, compound

HRID 448301Notes

Reaction equation

HRID 448301 reaction equation
[CH3:1][NH:2][CH3:3].C1COCC1.[Cl:9][CH2:10][C:11]([NH:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24])=[O:12]>CN(C=O)C>[ClH:9].[CH3:1][N:2]([CH3:3])[CH2:10][C:11]([NH:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24])=[O:12]

Participants

4

Reactant 2

HCID 22320367Dimethylamine tetrahydrofuranHCID 67229950HCID 67229950, compound

Product 1

HCID 67228906HCID 67228906, compoundYield 57.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Dimethylamine/THF (2M, 6.1 mL, 12.3 mmol) was added to a stirred solution of 2-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide (1.0 g, 3.1 mmol) in DMF (30 mL). The resulting solution was stirred at room temperature overnight. The mixture was concentrated, and the residue was stirred with CH2Cl2 (15 mL). The mixture was filtered, and the solid was dissolved in H2O (10 mL). 4N HCl (1.5 mL) was added and stirred for 30 minutes. The resulting solution was concentrated, and the residue was evaporated with ethanol (3×10 mL). The residue was slurried with ether (15 mL) and ethanol (5 mL). The mixture was filtered to give 2-dimethylamino-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide hydrochloride (0.7 g, 54%) as a white solid: mp 273-275° C.; 1H NMR (DMSO-d6) δ 2.00-2.04 (m, 1H), 2.33-2.65 (m, 2H), 2.81 (s, 6H, 2CH3), 2.87-3.01 (m, 1H), 4.02 (s, 2H, CH2), 4.36 (d, J=17.4 Hz, 1H), 4.43 (d, J=4.6 Hz, 2H, CH2), 4.55 (d, J=17.4 Hz, 1H), 5.12-5.19 (dd, J=5.0 and 13.1 Hz, 1H, CH), 7.48-7.67 (m, 3H, Ar), 9.41 (t, J=5.7 Hz, 1H, NH), 10.08 (s, 1H, NH), 11.04 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.60, 31.16, 39.06, 43.05, 46.19, 51.55, 57.07, 121.95, 128.32, 130.87, 131.72, 133.59, 140.25, 164.43, 167.93, 170.94, 172.84; Anal. calcd. for C18H23N4O4Cl+0.34H2O: C, 53.92; H, 5.95; N, 13.94; Cl, 8.84. Found: C, 54.06; H, 6.08; N, 13.72; Cl, 9.06.

Workup

  1. concentrationThe mixture was concentrated
  2. stirringthe residue was stirred with CH2Cl2 (15 mL)
  3. filtrationThe mixture was filtered
  4. dissolutionthe solid was dissolved in H2O (10 mL)
  5. addition4N HCl (1.5 mL) was added
  6. stirringstirred for 30 minutes
  7. concentrationThe resulting solution was concentrated
  8. customthe residue was evaporated with ethanol (3×10 mL)
  9. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-0775606f753546509a6f2edfc740329a
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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