Acetonitrile → 2-chloro-N-(3-(2,6-dioxopiperidin-3-yl)-2-methyl-4-oxo-3,4-dihydroquinazolin-5-yl)acetamide

HRID 1409625Notes

Reaction equation

HRID 1409625 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:21])[N:5]([CH:13]1[CH2:18][CH2:17][C:16](=[O:19])[NH:15][C:14]1=[O:20])[C:6]([CH3:12])=[N:7]2.[Cl:22][CH2:23][C:24](Cl)=[O:25].C(#N)C>CO>[Cl:22][CH2:23][C:24]([NH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:21])[N:5]([CH:13]1[CH2:18][CH2:17][C:16](=[O:19])[NH:15][C:14]1=[O:20])[C:6]([CH3:12])=[N:7]2)=[O:25]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 6577Chloroacetyl chlorideHCID 24967599Avadomide

Product 1

HCID 249683022-chloro-N-(3-(2,6-dioxopiperidin-3-yl)-2-methyl-4-oxo-3,4-dihydroquinazolin-5-yl)acetamideYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

The stirred mixture of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (4.0 g, 14 mmol) and chloroacetyl chloride (7.7 mL, 98 mmol) was heated in a 100° C. oil bath for 15 minutes. The mixture was allowed to cool to room temperature. Acetonitrile (5 mL) was added to the mixture. The suspension was filtered and washed with ethyl acetate (2×10 mL) to give a white solid. The solid was stirred in methanol (50 mL) overnight. The suspension was filtered and washed with methanol (20 mL) to give 2-chloro-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-yl]-acetamide as a white solid (4.5 g, 90% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 20/80 CH3CN/0.1% H3PO4, 12.79 min (97.6%); mp: 275-277° C.; 1H NMR (DMSO-d6) δ 2.18-2.25 (m, 1H, CHH), 2.61-2.80 (m, 5H, CH3, 2CHH), 2.86-2.91 (m, 1H, CHH), 4.48-4.53 (m, 2H, CH2), 5.36 (dd, J=6, 11 Hz, 1H, NCH), 7.39 (dd, J=1, 8 Hz, 1H, Ar), 7.83 (t, J=8 Hz, 1H, Ar), 8.57 (dd, J=1, 8 Hz, 1H, Ar), 10.7 (brs, 1H, HCl), 11.11 (s, 1H, NH), 12.26 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.66, 23.10, 30.60, 43.56, 56.84, 107.89, 115.65, 120.87, 135.77, 138.87, 147.17, 155.49, 162.67, 165.55, 169.14.172.60; LCMS: MH=363, 365; Anal Calcd for C16H15N4O4Cl+1.05 HCl: C, 47.92; H, 4.03; N, 13.97; Cl, 18.12. Found: C, 48.24; H, 3.79; N, 13.84; Cl, 18.27.

Workup

  1. temperatureto cool to room temperature
  2. filtrationThe suspension was filtered
  3. washwashed with ethyl acetate (2×10 mL)
  4. customto give a white solid
  5. filtrationThe suspension was filtered
  6. washwashed with methanol (20 mL)

Sources & evidence

ORD record
ord-c2294e1627d24509abe047bc26f5210e
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

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