Hydrochloric Acid → 2-dimethylamino-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-yl]-acetamide hydrogen chloride

HRID 1868247Notes

Reaction equation

HRID 1868247 reaction equation
[Cl:1][CH2:2][C:3]([NH:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[C:8](=[O:25])[N:9]([CH:17]1[CH2:22][CH2:21][C:20](=[O:23])[NH:19][C:18]1=[O:24])[C:10]([CH3:16])=[N:11]2)=[O:4].[CH3:26][NH:27][CH3:28].C1COCC1.C(=O)([O-])O.[Na+].Cl.CCOCC>CN(C=O)C.C(Cl)Cl.O>[ClH:1].[CH3:26][N:27]([CH3:28])[CH2:2][C:3]([NH:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[C:8](=[O:25])[N:9]([CH:17]1[CH2:22][CH2:21][C:20](=[O:23])[NH:19][C:18]1=[O:24])[C:10]([CH3:16])=[N:11]2)=[O:4]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 3283Diethyl EtherHCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 249683022-chloro-N-(3-(2,6-dioxopiperidin-3-yl)-2-methyl-4-oxo-3,4-dihydroquinazolin-5-yl)acetamide

Product 1

HCID 666428422-dimethylamino-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-yl]-acetamide hydrogen chlorideYield 85%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of 2-chloro-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-yl]-acetamide (0.75 g, 2.1 mmol) in DMF (3 mL), was added dimethylamine in THF (3.6 mL, 2N, 7.2 mmol) at room temperature. After 2 days, sodium hydrogen carbonate (sat, 10 mL) and water (10 mL) were added to the mixture. After 1 hour, the suspension was filtered and washed with water (5 mL) to give a white solid. To the stirred suspension of above solid in methylene chloride (20 mL), was added HCl in ether (2 mL, 2N, 4 mmol) at room temperature. After 18 hours, the suspension was filtered and washed with methylene chloride (2×20 mL) to give 2-dimethylamino-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-yl]-acetamide hydrogen chloride as a white solid (0.72 g, 85% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, 2.50 min (62.2%) and 2.71 (37.7%); mp: 256-258° C.; 1H NMR (DMSO-d6) δ 2.21-2.28 (m, 1H, CHH), 2.61-2.70 (m, 2H, 2CHH), 2.73 (s, 3H, CH3), 2.88 (s, 6H, 2CH2), 2.93-3.00 (m, 1H, CHH), 4.40 (d, J=4 Hz, 2H, CH2), 5.44 (dd, J=6, 11 Hz, 1H, NCH), 7.45 (dd, J=1, 8 Hz, 1H, Ar), 7.88 (t, J=8 Hz, 1H, Ar), 8.46 (dd, J=1.8 Hz, 1H, Ar), 10.48 (brs, 1H, HCl), 11.11 (s, 1H, NH), 11.50 (brs, 1H, HCl), 11.86 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.57, 23.04, 30.52, 43.16, 56.83, 58.16, 107.98, 116.49, 120.95, 135.94, 138.34, 146.82, 155.92, 162.45 163.75, 169.02, 172.63; LCMS: MH=372; Anal Calcd for C18H21N5O4+1.8HCl+0.5H2O: C, 48.47; H, 5.38; N, 15.70; Cl, 14.31. Found: C, 48.34; H, 5.03; N, 15.39; Cl, 14.03.

Workup

  1. waitAfter 1 hour
  2. filtrationthe suspension was filtered
  3. washwashed with water (5 mL)
  4. customto give a white solid
  5. waitAfter 18 hours
  6. filtrationthe suspension was filtered
  7. washwashed with methylene chloride (2×20 mL)

Sources & evidence

ORD record
ord-24b81d5e72df4d0bb75c2a1064d1485b
Source dataset
uspto-grants-2009_12
Patent number
US07635700B2

Reaction notes

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